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Deng F, Yang D, Qing L, Chen Y, Zou J, Jia M, Wang Q, Jiang R, Huang L. Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway: a potential therapeutic approach for neurodegenerative diseases. Neural Regen Res 2025; 20:3095-3112. [PMID: 39589173 PMCID: PMC11881707 DOI: 10.4103/nrr.nrr-d-24-00607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 08/07/2024] [Accepted: 09/10/2024] [Indexed: 11/27/2024] Open
Abstract
The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
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Affiliation(s)
- Fengcheng Deng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Dan Yang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lingxi Qing
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Yifei Chen
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Jilian Zou
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Meiling Jia
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Qian Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Runda Jiang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lihua Huang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
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Jin Y, Dong X, Zhong W, Xu C, Lin S, Peng Y, Jia B, Zhang J, Zhao X, Li H, Bian Y, Wang Y, Wang Y. ATF3 restoration as a potential strategy in managing ulcerative colitis: Implications from Sishen pill research. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 142:156814. [PMID: 40318535 DOI: 10.1016/j.phymed.2025.156814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 04/24/2025] [Accepted: 04/26/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited therapeutic options, particularly for moderate-to-severe cases. The present study evaluated the therapeutic potential of Sishen Pill (SSP) through Activating Transcription Factor 3 (ATF3). METHODS Colonic biopsy samples were collected from 11 UC patients and 6 healthy controls (HCs). A murine colitis model was established using dextran sodium sulfate (DSS) and treated with SSP. The therapeutic efficacy of SSP was evaluated by measuring body weight, colonic length, and inflammatory markers in wild-type (WT) mice. Transcriptomic analysis revealed differentially expressed genes in colonic tissues following Atf3 knockout. Western blotting, immunofluorescence, immunohistochemical, and Luminex assays were conducted to assess the effect of SSP on Neutrophil Extracellular Traps (NETs) formation and ATF3 signaling. RESULTS ATF3 expression was significantly reduced in the inflamed mucosa of UC patients, correlating with disease severity. UC tissues also exhibited increased spontaneous NETs formation. In DSS-induced colitis mice, ATF3 expression was similarly reduced, whereas SSP treatment upregulated ATF3, mitigated weight loss, reduced colonic shortening, alleviated histopathological damage, and lowered inflammatory cytokine levels. Atf3 knockout mice (Atf3-/-) displayed more severe DSS-induced colitis with enhanced immune response as compared to control littermates (Atf3+/+). Transcriptomic analyses revealed that SSP downregulated key genes involved in NETs formation pathways, tumor necrosis factor (TNF) and cytokine-cytokine receptor signaling. Experimental validation confirmed that SSP reduced the levels of NETs-related proteins [Myeloperoxidase (MPO), Peptidylarginine Deiminase 4 (PAD4), Lymphocyte Antigen 6 Complex, G (Ly6G), Neutrophil Elastase (NE), Citrullinated Histone H3 (CitH3)] in the colorectal tissue of colitis mice. It also down-regulated TNF pathway-related proteins [Phosphorylated Extracellular Signal-Regulated Kinase (p-ERK), Matrix Metalloproteinase 9 (MMP9)]. Furthermore, SSP intervention reduced pro-inflammatory factors [interleukin (IL)-6, IL1β, Granulocyte Colony-Stimulating Factor (G-CSF) and TNF-α] and decreased CXCL1/CXCR2 axis factors, including CXCL1 protein levels and diminished CXCR2+MPO+ positive expressed cells. Importantly, these beneficial effects of SSP were ATF3-dependent, as SSP did not exert its effects in Atf3-/- mice. CONCLUSION SSP ameliorates colitic mice through multiple mechanisms, including the inhibition of NETs formation, attenuation of inflammatory responses, and suppression of CXCL1/CXCR2-mediated inflammation, all via modulation of ATF3 expression. These findings support the potential of SSP as a promising adjunctive therapy for UC and underscore the therapeutic potential of targeting ATF3 in future treatment strategies.
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Affiliation(s)
- Yutong Jin
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Xuetao Dong
- Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China
| | - Weilong Zhong
- Tianjin Key Laboratory of Digestive Diseases, Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, PR China
| | - Chen Xu
- Department of Colorectal Surgery, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China
| | - Shan Lin
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Yanfei Peng
- School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Beitian Jia
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Jiani Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China
| | - Xiaoxu Zhao
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Huihui Li
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Yuhong Bian
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
| | - Yue Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
| | - Yao Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China.
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Salem MB, El-Lakkany NM, Hammam OA, Seif el-Din SH. Bacillus clausii spores maintain gut homeostasis in murine ulcerative colitis via modulating microbiota, apoptosis, and the TXNIP/NLRP3 inflammasome cascade. Toxicol Rep 2025; 14:101858. [PMID: 39802600 PMCID: PMC11721221 DOI: 10.1016/j.toxrep.2024.101858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/04/2024] [Accepted: 12/08/2024] [Indexed: 01/16/2025] Open
Abstract
Ulcerative colitis (UC), a persistent immune-mediated disorder lacking effective treatment, is distinguished by gut microbiota dysbiosis, abnormal activation of the NLRP3 inflammasome pathway, and apoptosis. Despite growing attention to these factors, understanding their significance in UC pathogenesis remains a challenge. The present study explores the potential therapeutic impact of Bacillus clausii (Bc) spores in a murine UC model induced by drinking 4 % (w/v) dextran sulfate sodium (DSS) in C57BL/6 mice. Subsequently, the DSS-induced mice were orally administered either Bc at varying concentrations (105 and 1010 Colony forming unit, CFU) or sulfasalazine (SSZ) at a dosage of 200 mg/kg for 7 days. The disease-specific activity index (DAI) was calculated daily utilizing parameters such as body weight, diarrhea, and bloody stool. Changes in fecal Firmicutes and Bacteroidetes abundance, colonic TXNIP and NLRP3 contents, as well as colonic caspase-1, IL-1β, Bax, and Bcl-2 expression, were investigated. Additionally, markers related to oxidative stress and inflammation, histopathological changes and caspase-3 immunohistochemistry testing were conducted. DSS-treated mice had significantly higher DAI scores compared to controls, indicating severe colitis. However, SSZ treatment or Bc (105 CFU) dramatically lowered DAI scores, with the highest Bc dosage (1010 CFU) producing the greatest improvement. Furthermore, Bc (1010 CFU) substantially (p < 0.05) boosted fecal Firmicutes while decreased Bacteroidetes, indicating reversal of gut dysbiosis. Bc effectively reduced colonic oxidative stress and inflammation by replenishing GSH and catalase and modulating the NF-κB, Nrf2/HO-1, and TXNIP/NLRP3 pathways. Additionally, Bc (1010 CFU) exhibited histologically almost normal mucosa, with maintained architecture and reduced apoptosis, as seen by normalization of Bcl2 and Bax with decreased caspase-3. Collectively, these findings point to the potential usefulness of Bc spores in preventing and treating DSS-induced colitis, positioning them as a promising candidate for UC management.
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Affiliation(s)
- Maha B. Salem
- Pharmcology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | | | - Olfat A. Hammam
- Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt
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Wang H, Yang Y, Li T, Chang S, Zhu Y, Liu C. Drinking Water Temperature Impacts the Pathogenesis of DSS-Induced Ulcerative Colitis by Regulating Intestinal Barrier Function and Remodeling the Gut Microbiota Composition. FASEB J 2025; 39:e70645. [PMID: 40377203 DOI: 10.1096/fj.202500062r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 04/18/2025] [Accepted: 05/07/2025] [Indexed: 05/18/2025]
Abstract
Environmental factors, including poor dietary habits and unhealthy drinking patterns, contribute to ulcerative colitis (UC). While the relationship between diet-related malnutrition and UC has been extensively explored, the impact of drinking water temperature remains largely overlooked, prompting us to investigate its influence on UC pathogenesis and explore the underlying mechanisms. In the present study, we observed that, unlike external thermal and cold therapy, varying drinking water temperatures transiently altered the internal body temperature of the digestive tract. Specifically, chronic drinking of 0°C water had significant anti-inflammatory effects and preserved the integrity of the mucosal barrier in a colitis mouse model. Mechanistically, this temperature spectrum changed the composition of the gut microbiota from inflammation-prone (25°C drinking water) to a resting pattern similar to that of the negative control. Specifically, the abundances of Blautia and Parasutterella, two beneficial genera, were strongly increased in response to 0°C water, accompanied by elevated levels of short-chain fatty acids. In contrast, drinking 40°C water had opposite effects on all the examined parameters and generally aggravated the development of colitis. This study is the first to demonstrate how modifying the temperature of habitual drinking water can modulate colitis progression, providing a novel and noninvasive approach to UC management. Specifically, chronic consumption of 0°C water alleviated the severity of colitis, whereas 40°C water aggravated the disease. Therefore, by focusing on commonly consumed drinking water temperatures, our findings suggest that this simple intervention could be a safe, convenient, and effective therapeutic strategy.
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Affiliation(s)
- Huiting Wang
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Yiheng Yang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tianyu Li
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Shengyu Chang
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Yao Zhu
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Chang Liu
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
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Xu Z, Zhao L, Wu M, Cui A, Chen W, Zheng G, Zhou J, Gao D, Shi R. Prophylactic administration of overproducing-abscisic acid Bacillus licheniformis attenuated DSS-induced colitis in mice by regulating the gut microbiota and immune activity. BMC Microbiol 2025; 25:306. [PMID: 40389822 PMCID: PMC12087060 DOI: 10.1186/s12866-025-03988-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 04/23/2025] [Indexed: 05/21/2025] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) involves the complex interplay among the mucosal barrier, microbiota, immunity and genetic factors. There are currently no satisfactory treatments for IBD. Administration of the probiotic Bacillus licheniformis (Bl) can improves colitis by regulating the gut microbiota. The phytohormone abscisic acid (ABA) treatment has favorable effects on immunity, as well as on inflammatory diseases like colitis. We hypothesized that the expression of an additional cyp gene by the Bl to increase its ABA production would enhance its effects. RESULTS In this study, we found that a Bl-cyp strain overexpressing the cyp gene secreted more ABA into its supernatant than either the parental Bl stain or a Bl-pET82a strain expressing only a vector pET82a when these bacteria were grown in Nfb medium for 48 h. The prophylactic administration of the Bl-cyp strain culture more effectively attenuated dextran sodium sulfate (DSS)-induced colitis in mice compared to the Bl and Bl-pET28a strains. These findings were associated with significantly reduced epithelial barrier damage, as well as increased number of goblet cells and expression levels of occludin gene in the colonic epithelial layer, and decreased serum LPS levels in the Bl-cyp group. In addition, the administration of Bl-cyp strain effectively regulated the disordered gut microbiota by improving their diversity, richness and compositions more than the Bl or Bl-pET82a strain, including the ratio of Bacteroidota: Bacillota. It also inhibited the excessive growth of opportunistic pathogen Escherichia just like the Bl or Bl-pET82a strain. Moreover, the preventive administration of the Bl-cyp strain to mice following DSS-induced colitis enhanced the proportion of Treg cells and suppressed the proportion of Th17 cells in mesenteric lymph nodes (MLNs), decreased the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-22, and increased the level of anti-inflammatory IL-10 in colon tissues, similar to treatment with a high concentration of the ABA standard (ABA-H). Notably, the treatment with the Bl-cyp strain more effectively regulated the disordered microbiota than the ABA-H. CONCLUSIONS The administration of the Bl-cyp strain may provide a novel preventive approach for IBD, and may exert its effects by modulating the gut microbiota and host's immune status.
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Affiliation(s)
- Zeyan Xu
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Lijiang Zhao
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Mengting Wu
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Anqi Cui
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Wei Chen
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Guohao Zheng
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Jingyi Zhou
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China
| | - Daqing Gao
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
| | - Ruihua Shi
- School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
- Department of Gastroenterology, Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu, 210009, China.
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Schimmele T, Langgartner D, Gebauer D, Mazzari G, Probst J, Weingast G, Ignatius A, Tabacco G, Naciu AM, Messina MV, Palermo A, Reber SO, Haffner-Luntzer M. Early life adversity promotes a milieu in favor of catabolic bone turnover in females: Mycobacterium vaccae NCTC 11659 proofs protective in preclinical studies. Brain Behav Immun 2025:S0889-1591(25)00187-4. [PMID: 40383402 DOI: 10.1016/j.bbi.2025.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 05/07/2025] [Accepted: 05/12/2025] [Indexed: 05/20/2025] Open
Abstract
Despite early clinical studies supporting the hypothesis that early life adversity (ELA) negatively affects the bone and despite typical ELA-associated disorders, including post-traumatic stress disorder (PTSD) and major depressive disorder (MD), are associated with osteoporosis and increased bone fracture risk, preclinical studies do not support this association. However, previous studies were only performed using male and not female mice. In the current study we showed that ELA, induced by the classical maternal separation (MS) paradigm, facilitated femoral osteoclast activity specifically in female but not male mice. This was associated with a transient decline in both intestinal alpha diversity and Firmicutes/Bacteroidetes ratio, suggesting that the microbiome-gut-bone axis is involved in these effects. Moreover, ELA long-lastingly increased the femoral mRNA expression of the proinflammatory cytokine Interleukin-6 (IL-6) and the osteoclastic markers Cathepsin K and RANKL. Importantly, all sex-specific ELA effects on bone were absent in female mice administered with M. vaccae NCTC 11659 following ELA exposure. Finally, our clinical data indicate strong associations between ELA and development of an osteopenic/osteoporotic bone phenotype in postmenopausal women undergoing bone diagnostics. Together, our preclinical and clinical findings indicate that i) ELA negatively affects the bone, ii) these effects are specific for female sex, iii) the negative effects of ELA on female bone are associated with transient changes in the composition of the intestinal microbiome followed by long-lasting activation of the immune system and the HPA axis, together setting the stage for a facilitated catabolic bone turnover and development of an osteopenic/osteoporotic bone phenotype, iv) developing immunoregulatory approaches, such as repeated s.c. administrations with immunoregulatory microorganisms, have potential for prevention/treatment of ELA-related bone disorders.
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Affiliation(s)
- Tamara Schimmele
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89081 Ulm, Germany
| | - Dominik Langgartner
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89081 Ulm, Germany
| | - Dorothea Gebauer
- Institute of Orthopaedic Research and Biomechanics, Ulm University Medical Center, Germany
| | - Giulia Mazzari
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89081 Ulm, Germany
| | - Julian Probst
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89081 Ulm, Germany
| | - Giulia Weingast
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89081 Ulm, Germany
| | - Anita Ignatius
- Institute of Orthopaedic Research and Biomechanics, Ulm University Medical Center, Germany
| | - Gaia Tabacco
- Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Anda Mihaela Naciu
- Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Maria Vittoria Messina
- Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Andrea Palermo
- Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - Stefan O Reber
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89081 Ulm, Germany; Institute of Orthopaedic Research and Biomechanics, Ulm University Medical Center, Germany; German Center for Mental Health (DZPG), partner site Mannheim//-Heidelberg//-Ulm, Germany.
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Hsu CY, Ahmad I, Maya RW, Abass MA, Gupta J, Singh A, Joshi KK, Premkumar J, Sahoo S, Khosravi M. The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review. J Transl Med 2025; 23:530. [PMID: 40350437 PMCID: PMC12066075 DOI: 10.1186/s12967-025-06527-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Accepted: 04/21/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS. METHODS The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including "ME/CFS," "Gut-Brain Axis," "Gut Health," "Intestinal Dysbiosis," "Microbiome Dysbiosis," "Pathophysiology," and "Therapeutic Approaches." Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings. RESULTS The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration. CONCLUSIONS Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.
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Affiliation(s)
- Chou-Yi Hsu
- Thunderbird School of Global Management, Arizona State University, Tempe Campus, Phoenix, AZ, USA
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | | | | | - Jitendra Gupta
- Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Abhayveer Singh
- Centre for Research Impact & Outcome, Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, India
| | - Kamal Kant Joshi
- Department of Allied Science, Graphic Era Hill University, Dehradun, India
- Graphic Era (Deemed to Be University), Dehradun, Uttarakhand, India
| | - J Premkumar
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Samir Sahoo
- Department of General Medicine, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, India
| | - Mohsen Khosravi
- Department of Psychiatry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
- Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
- Community Nursing Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
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Chen Z, Li L, Guo L, Kang C, Cui X, Pu S, Wang C, Yang Y. A Gastrodia elata polysaccharide for restoring intestinal immunocompromise. Int J Biol Macromol 2025; 307:141781. [PMID: 40054798 DOI: 10.1016/j.ijbiomac.2025.141781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/21/2025] [Accepted: 03/04/2025] [Indexed: 03/17/2025]
Abstract
We here extracted a polysaccharide fragment from Gastrodia elata, characterized by a main chain connected via (1 → 4)-α-D-Glcp bonds, with terminal α-D-Glcp-(1→) linked to the main chain through O-6 of (1 → 4,6)-α-D-Glcp and O-3 of (1 → 3,4)-α-D-Glcp (SRGP). Both in vitro and in vivo experiments demonstrated that SRGP activates the TLR4/NF-κB signaling pathway, exerting immunomodulatory effects and alleviating cyclophosphamide (CTX)-induced intestinal mucosal damage in mice. High-throughput 16S rRNA sequencing further revealed that SRGP restores gut microbiota composition and enhances the abundance of specific bacterial populations. Additionally, SRGP improves CTX-induced intestinal mucosal damage by upregulating tight junction proteins, mitigating gut microbiota dysbiosis, and regulating both the overall microbial community and the levels of specific bacteria.
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Affiliation(s)
- Zhuowen Chen
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Ling Li
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Lanping Guo
- China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Chuanzhi Kang
- China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Xiuming Cui
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Shulin Pu
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Chengxiao Wang
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China.
| | - Ye Yang
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China.
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Ma QS, Chen QL, Wu GP, Yao YW, Fan YX, Linghu KG, Chen JM, Xiong W, Yu H. Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway. Front Pharmacol 2025; 16:1588525. [PMID: 40356967 PMCID: PMC12066544 DOI: 10.3389/fphar.2025.1588525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Accepted: 04/15/2025] [Indexed: 05/15/2025] Open
Abstract
Background Ulcerative colitis (UC) is a prevalent immune-mediated inflammatory bowel disease characterized by mucus secretion, hematochezia, and diarrhea. This study compared the therapeutic effects of three Siegesbeckiae Herba (SH) species used in traditional Chinese medicine-Sigesbeckia orientalis L (SO), Sigesbeckia pubescens Makino (SP), and Sigesbeckia glabrescens Makino (SG) - in dextran sulfate sodium (DSS)-induced UC mice. Methods UC was induced in C57BL/6 mice with 3% DSS for 7 days. Cytokine levels in serum and colon tissues were measured by enzyme-linked immunosorbent assay. Protein and gene expression were analyzed using Western blotting and PCR. Histopathological changes were assessed via hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence. Fecal specimens were collected for gut microbiota analysis. An in vitro UC model was also established in NCM460 cells using lipopolysaccharide (LPS), and Caco-2 cells were used to examine intestinal mucosal integrity. Results SP substantially decreased the disease activity index, enhanced colon shortening, and mitigated histological damage in comparison to the model group. Mechanistic investigations demonstrated that SP functioned via the activation of the Nrf2/Keap1 pathway, markedly increased the activity of the antioxidant enzyme glutathione in colon tissues, decreased the concentration of the oxidative marker malondialdehyde, and upregulated the expression of the downstream genes H O -1 and NQO1. Conclusion The study reveals for the first time the differences in efficacy of different species of SH and its molecular mechanism, demonstrating that SP increases oxidative defense via the activation of the Nrf2/Keap1 pathway, therefore mitigating colitis and oxidative damage in UC mice. This discovery not only establishes a scientific foundation for the selective preference of SH species but also offers a novel technique for the creation of natural pharmaceuticals aimed at the Nrf2 pathway for the treatment of UC.
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Affiliation(s)
- Qiu-Shuo Ma
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
| | - Qi-Ling Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
| | - Guo-Ping Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
| | - Ya-Wen Yao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
| | - Yu-Xin Fan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
| | - Ke-Gang Linghu
- The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City, Guizhou, China
| | - Jun-Ming Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
| | - Wei Xiong
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, China
| | - Hua Yu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
- Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China
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Ahmadi A, Shokoohizadeh L, Sheikhesmaili F, Mirzaei MK, Mohammadi A, Nikkhoo B, Khodaei H, Alikhani MY, Yousefimashouf R. Gut microbiomes and treatment-resistant ulcerative colitis: a case-control study using qPCR. BMC Microbiol 2025; 25:254. [PMID: 40295906 PMCID: PMC12036124 DOI: 10.1186/s12866-025-03963-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 04/14/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND The gut microbiome has been identified as a pivotal factor in ulcerative colitis (UC), given its role as the main reservoir of microbes in the body. This community of microorganisms, present in variable concentrations in the digestive tract, makes a wide range of beneficial roles for the host. However, the role of the gut microbiome in patients with refractory UC is still significant, so this study aimed to further investigate the role of these bacteria in patients with refractory UC. METHODS This case-control study was conducted on stool samples from four distinct groups: the first group comprised new patients diagnosed with ulcerative colitis (all of them had responded to treatment after follow-up) (N = 24); the second group consisted of patients with treatment-resistant ulcerative colitis (N = 23); the third group included first-degree relatives of group 1 patients (N = 24); and the fourth group consisted of first-degree relatives of group 2 patients (N = 23). The research tools employed in this study included a questionnaire, quantitative real-time PCR (qPCR) test, and culture on stool samples. RESULT The mean age of patients in groups 1 and 2 was 45.88 ± 18.51 and 41.30 ± 13.01 years, while the mean age of controls in groups 3 and 4 was 37.29 ± 9.62 and 40.96 ± 13.01 years, respectively. Stool culture results for pathogenic bacteria were negative in all four groups. The of history of consuming dairy products containing probiotics was highest in Group 1, with 22 (91.67%) subjects, while the lowest was observed in Group 3, with 16 (66.67%). The highest history of self-administered antibiotic use was observed in Group 2, with 13 cases (56.52%), while the lowest was noted in Group 3, with 4 cases (16.67%). The findings indicated a statistically significant relationship (P < 0.05) between Groups 2 and 4 with respect to the E. coli and Bifidobacterium ssp. microbial population. Additionally, a significant relationship was identified between the Lactobacillus ssp., Bifidobacterium ssp., and Bacteroides ssp. microbial community between groups 1 and 2 (P < 0.05). CONCLUSION The findings of this study demonstrated that several intestinal microbiomes have a substantial impact on the management of ulcerative colitis. The results of this study suggest that by comparing the gut microbiome of treatment-resistant and individuals newly diagnosed with ulcerative colitis, we can gain a better understanding of microbiome differences that may influence treatment outcomes. The results of this study may also lead to the identification of new therapeutic strategies that are based on regulating the gut microbiome. These strategies could include the use of fecal microbiome transplantation (FMT), probiotics, prebiotics, or specific bacteria-based therapies.
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Affiliation(s)
- Amjad Ahmadi
- Infectious Disease Research Center, Avicenna Institute of Clinical Sciences, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Leili Shokoohizadeh
- Infectious Disease Research Center, Avicenna Institute of Clinical Sciences, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Farshad Sheikhesmaili
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mohammadali Khan Mirzaei
- Institute of Virology, Helmholtz Munich, German Research Centre for Environmental Health, Neuherberg, Germany
- Chair of Prevention of Microbial Infectious Diseases, Central Institute of Disease Prevention, School of Life Sciences, Technical University of Munich, Freising, Germany
| | - Asadollah Mohammadi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Bahram Nikkhoo
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Hakim Khodaei
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mohammad Yousef Alikhani
- Infectious Disease Research Center, Avicenna Institute of Clinical Sciences, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran.
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Rasoul Yousefimashouf
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
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11
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Zhu S, Yang Z, Liu Y, Cheng L, Long D, Dai F. Oral Lipid Nanoparticles for Improving the Efficiency of Drug Delivery Systems in Ulcerative Colitis: Recent Advances and Future Prospects. Pharmaceutics 2025; 17:547. [PMID: 40430840 PMCID: PMC12114620 DOI: 10.3390/pharmaceutics17050547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/12/2025] [Accepted: 04/19/2025] [Indexed: 05/29/2025] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent, recurrent, and relapsing inflammation of the mucosal layer. Its pathogenesis is complex and not yet fully understood, with current treatments mainly focused on alleviating symptoms through pharmacological methods. Direct drug administration for UC often leads to poor intestinal bioavailability, suboptimal targeting, and an increased risk of resistance. Therefore, there is an urgent need for effective drug delivery systems. Lipid nanoparticles (LNPs) are promising candidates for UC drug delivery due to their high biocompatibility, stability, and customizable properties. Oral administration, as a preferred treatment approach for UC, offers benefits such as convenience, cost-effectiveness, and better patient compliance. However, oral drug delivery systems must navigate the complex gastrointestinal tract to effectively target colonic lesions, posing significant challenges for LNP-based systems. Researchers are exploring ways to enhance oral delivery efficiency by adjusting LNP composition, surface functionalization, and coating. This article reviews recent advancements in oral LNP research aimed at improving drug delivery efficiency for UC treatment and discusses future prospects.
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Affiliation(s)
- Siyu Zhu
- State Key Laboratory of Resource Insects, Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, Southwest University, Chongqing 400715, China; (S.Z.); (Z.Y.); (Y.L.); (L.C.)
- College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China
| | - Zhenlin Yang
- State Key Laboratory of Resource Insects, Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, Southwest University, Chongqing 400715, China; (S.Z.); (Z.Y.); (Y.L.); (L.C.)
| | - Yulong Liu
- State Key Laboratory of Resource Insects, Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, Southwest University, Chongqing 400715, China; (S.Z.); (Z.Y.); (Y.L.); (L.C.)
| | - Lan Cheng
- State Key Laboratory of Resource Insects, Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, Southwest University, Chongqing 400715, China; (S.Z.); (Z.Y.); (Y.L.); (L.C.)
- College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China
- Yibin Academy of Southwest University, Yibin 644000, China
| | - Dingpei Long
- State Key Laboratory of Resource Insects, Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, Southwest University, Chongqing 400715, China; (S.Z.); (Z.Y.); (Y.L.); (L.C.)
- College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China
- Yibin Academy of Southwest University, Yibin 644000, China
| | - Fangyin Dai
- State Key Laboratory of Resource Insects, Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, Southwest University, Chongqing 400715, China; (S.Z.); (Z.Y.); (Y.L.); (L.C.)
- College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China
- Yibin Academy of Southwest University, Yibin 644000, China
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12
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Bonomo MG, D’Angelo S, Picerno V, Carriero A, Salzano G. Recent Advances in Gut Microbiota in Psoriatic Arthritis. Nutrients 2025; 17:1323. [PMID: 40284188 PMCID: PMC12030176 DOI: 10.3390/nu17081323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/04/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025] Open
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.
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Affiliation(s)
- Maria Grazia Bonomo
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
| | - Salvatore D’Angelo
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Valentina Picerno
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Antonio Carriero
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Via Potito Petrone, 85100 Potenza, Italy; (V.P.); (A.C.)
| | - Giovanni Salzano
- Department of Health Sciences, University of Basilicata, Viale dell’ Ateneo Lucano 10, 85100 Potenza, Italy; (S.D.); (G.S.)
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13
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Lu X, Sun Y, Zhang Z, Sun Z, Wang S, Xu E. Regulation of pyroptosis by natural products in ulcerative colitis: mechanisms and therapeutic potential. Front Pharmacol 2025; 16:1573684. [PMID: 40271055 PMCID: PMC12014637 DOI: 10.3389/fphar.2025.1573684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Accepted: 03/31/2025] [Indexed: 04/25/2025] Open
Abstract
Ulcerative colitis (UC), a chronic inflammatory bowel disease, is driven by dysregulated immune responses and persistent intestinal inflammation. Pyroptosis, a caspase/gasdermin-mediated inflammatory cell death that exacerbates mucosal damage through excessive cytokine release and epithelial barrier disruption. Although pyroptosis is considered to be a key mechanism in the pathogenesis of UC, the systematic assessment of the role of natural products in targeting the pyroptosis pathway remains a critical research gap. The purpose of this review is to investigate the regulatory effects of natural products on pyroptosis in UC and elucidate the mechanisms of action and potential therapeutic effects. Key findings highlight polyphenols (e.g., resveratrol), flavonoids (e.g., Quercetin), and terpenoids as promising agents that inhibit NLRP3 inflammasome activation, suppress gasdermin D cleavage, and restore barrier integrity, thereby reducing pro-inflammatory cytokine release in preclinical UC models. Current evidence shows enhanced efficacy and safety when these compounds are combined with standard therapies, but clinical translation requires overcoming three key barriers: limited human trial data, uncharacterized polypharmacology, and suboptimal pharmacokinetics needing formulation refinement. Future research should prioritize standardized animal-to-human translational models, mechanistic studies on synergistic pathways, and rigorous clinical validation to harness the full potential of natural products in pyroptosis-targeted UC therapies.
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Affiliation(s)
- Xiaobei Lu
- Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yapeng Sun
- Department of Proctology, Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Zhaoyi Zhang
- Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, Zhengzhou, China
| | - Zhigang Sun
- Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, Zhengzhou, China
| | - Shaohui Wang
- Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, China
| | - Erping Xu
- Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chinese Medicine, Zhengzhou, China
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14
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Fatahi S, Sohouli MH, Vahidshahi K, Rohani P, Safa M, Salehi M, Găman MA, Shidfar F. Changes in gut microbiota following supplementation with chitosan in adolescents with overweight or obesity: a randomized, double-blind clinical trial. Diabetol Metab Syndr 2025; 17:120. [PMID: 40200345 PMCID: PMC11978168 DOI: 10.1186/s13098-025-01681-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 03/24/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Overweight and obesity have been associated with an altered intestinal microbiome. Recent investigations have demonstrated that fiber supplementation, including chitosan, can exert beneficial and protective effects on the composition of gut microbiota in humans diagnosed with overweight/obesity. However, there is still a great deal of heated debate regarding the impact of chitosan supplementation in overweight and obese adolescents. Therefore, the aim of this study is to clarify the effects of chitosan administration on the composition of the gut microbiome in overweight and obese adolescents. METHODS AND ANALYSIS Sixty-four overweight and obese adolescents were subjected to supplementation with 3 g of chitosan for 12 weeks. Anthropometric indices and physical activity were measured at the beginning and at the end of the intervention. After DNA extraction and purification, the quantity of bacteria in the patients' stool samples was determined by real-time polymerase chain reaction (PCR). The RCT was registered on the Iranian Registry of Clinical Trials ( www.irct.ir ) website (IRCT20091114002709 N57; registration date: 2021 - 06 - 20). RESULTS Individuals who received chitosan supplementation experienced a significant decrease in the BMI z-score (P < 0.001). Administration of chitosan led to notable significant decrease in the Firmicutes (P < 0.001) populations and the ratio of Firmicutes to Bacteroidetes (P < 0.001) as well as a notable increase in the Bacteroidetes (P = 0.008) and Akkermansia (P < 0.001) populations, respectively compare to control group. Mean changes in Lactobacillus populations were marginally significant (P = 0.05). Chitosan administration did not alter the composition in Bifidobacterium populations (P = 0.97). CONCLUSION The present study demonstrates beneficial effects of chitosan administration on some bacterial species associated with overweight and obesity in adolescents. Further research is needed to confirm our findings and clarify the impact of this intervention on the Lactobacillus population in the gut.
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Affiliation(s)
- Somaye Fatahi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hassan Sohouli
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children'S Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Koroush Vahidshahi
- Department of Pediatrics, School of Medicine, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children'S Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Majid Safa
- Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoud Salehi
- Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mihnea-Alexandru Găman
- Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Farzad Shidfar
- Faculty of Public Health Branch, Department of Nutrition, Iran University of Medical, Sciences, Tehran, Iran.
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15
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Nista EC, Parello S, Brigida M, Amadei G, Saviano A, De Lucia SS, Petruzziello C, Migneco A, Ojetti V. Exploring the Role of Gut Microbiota and Probiotics in Acute Pancreatitis: A Comprehensive Review. Int J Mol Sci 2025; 26:3433. [PMID: 40244415 PMCID: PMC11989318 DOI: 10.3390/ijms26073433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/02/2025] [Accepted: 04/04/2025] [Indexed: 04/18/2025] Open
Abstract
Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation.
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Affiliation(s)
- Enrico Celestino Nista
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Simone Parello
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Mattia Brigida
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy;
| | - Giulio Amadei
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Angela Saviano
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Sara Sofia De Lucia
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | | | - Alessio Migneco
- Fondazione Policlinico Gemelli, Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy; (E.C.N.); (S.P.); (G.A.); (A.S.); (S.S.D.L.); (A.M.)
| | - Veronica Ojetti
- Ospedale San Carlo di Nancy, GVM Research, 00165 Rome, Italy
- Department of Internal Medicine, UniCamillus International Medical University of Rome, 00131 Rome, Italy
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Rajbhandari RM, Forcina G, Manandhar P, Rajbhandari PG, Napit R, Raut R, Shrestha S, Sadaula A, Gortázar C, Alves PC, de la Fuente J, Queirós J, Karmacharya D. Gut microbiota diversity among humans, elephants, livestock and wild herbivores in Chitwan National Park bears implications for conservation medicine. Sci Rep 2025; 15:11596. [PMID: 40185849 PMCID: PMC11971256 DOI: 10.1038/s41598-025-89402-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 02/05/2025] [Indexed: 04/07/2025] Open
Abstract
Gut microbiome influences host health and well-being. Co-occurring hosts may exchange disease-causing bacteria belonging to these microbial communities. Therefore, monitoring gut microbiota composition in wildlife and humans is paramount to prevent zoonotic diseases, thus protecting and strengthening public health. We characterized diversity and abundance of the gut microbiome bacterial component across mahouts (captive elephant trainers and handlers), their pachyderms, livestock and wild herbivores in and around Chitwan National Park (Nepal). Firmicutes and Bacteroidota were invariably the dominant phyla. In humans, the relative abundance of Firmicutes was higher, the alpha diversity lower and beta diversity different compared to other host categories. Livestock and wild herbivores displayed similar alpha and beta diversity due to the presence of Proteobacteria, Actinobacteriota and Verrucomicrobiota. Elephants had a higher alpha diversity, and a significant beta diversity compared to other mammals. Our results suggest that taxonomic affiliation and diet niche are the main drivers of gut microbiota composition. Nevertheless, Mycobacterium and other potentially pathogenic bacteria genera were detected in elephants and livestock other than wild herbivores. These findings shed light on microbiota sharing and interlinking in each environment, thereby highlighting the importance of conservation medicine to better our understanding of health in co-occurring host species.
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Affiliation(s)
- Rajesh Man Rajbhandari
- Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
- CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus de Vairão, Universidade do Porto, Vairão, Portugal
- BIOPOLIS Program in Genomics, Biodiversity and Land Planning, Campus de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal
- Institute for Game and Wildlife Research, IREC (CSIC-UCLM-JCCM), SaBio Research Group, Ciudad Real, Spain
- Center for Molecular Dynamics Nepal, Swaraj Sadhan, Thapathali 11, Kathmandu, Nepal
| | - Giovanni Forcina
- CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus de Vairão, Universidade do Porto, Vairão, Portugal
- BIOPOLIS Program in Genomics, Biodiversity and Land Planning, Campus de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal
- Departamento de Ciencias de la Vida, Global Change Ecology and Evolution (GloCEE) Group and Research Team on Soil Biology and Subterranean Ecosystems (GIBSES), Universidad de Alcalá (UAH), Alcalá de Henares, Madrid, Spain
| | - Prajwol Manandhar
- Center for Molecular Dynamics Nepal, Swaraj Sadhan, Thapathali 11, Kathmandu, Nepal
| | - Pragun G Rajbhandari
- Center for Molecular Dynamics Nepal, Swaraj Sadhan, Thapathali 11, Kathmandu, Nepal
| | - Rajindra Napit
- Center for Molecular Dynamics Nepal, Swaraj Sadhan, Thapathali 11, Kathmandu, Nepal
| | - Roji Raut
- Center for Molecular Dynamics Nepal, Swaraj Sadhan, Thapathali 11, Kathmandu, Nepal
| | - Seily Shrestha
- Center for Molecular Dynamics Nepal, Swaraj Sadhan, Thapathali 11, Kathmandu, Nepal
| | - Amir Sadaula
- Biodiversity Conservation Center, National Trust for Nature Conservation, Sauraha, Chitwan, Nepal
| | - Christian Gortázar
- Institute for Game and Wildlife Research, IREC (CSIC-UCLM-JCCM), SaBio Research Group, Ciudad Real, Spain
| | - Paulo Célio Alves
- Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
- CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus de Vairão, Universidade do Porto, Vairão, Portugal
- BIOPOLIS Program in Genomics, Biodiversity and Land Planning, Campus de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal
- EBM, Estação Biológica de Mértola, Praça Luís de Camões, 7750-329, Mértola, Portugal
| | - José de la Fuente
- Institute for Game and Wildlife Research, IREC (CSIC-UCLM-JCCM), SaBio Research Group, Ciudad Real, Spain
- Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA
| | - João Queirós
- Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
- CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus de Vairão, Universidade do Porto, Vairão, Portugal
- BIOPOLIS Program in Genomics, Biodiversity and Land Planning, Campus de Vairão, Universidade do Porto, 4485-661, Vairão, Portugal
- EBM, Estação Biológica de Mértola, Praça Luís de Camões, 7750-329, Mértola, Portugal
| | - Dibesh Karmacharya
- Center for Molecular Dynamics Nepal, Swaraj Sadhan, Thapathali 11, Kathmandu, Nepal.
- School of Biological Sciences, Faculty of Science, The University of Queensland, Brisbane, Australia.
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Chen W, Xu L, Wang L, Shan YN, Li Y, Zhu JS. Qing-Re-Hua-Shi Decoction ameliorates DSS-induced colitis by modulating multiple signaling pathways and remodeling the gut microbiota and metabolite profile. Front Cell Infect Microbiol 2025; 15:1541289. [PMID: 40242025 PMCID: PMC11999956 DOI: 10.3389/fcimb.2025.1541289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 03/13/2025] [Indexed: 04/18/2025] Open
Abstract
Background Clinically, Qing-Re-Hua-Shi Decoction (QRHSD) has been clinically used to treat ulcerative colitis (UC) with satisfactory outcomes and minimal side effects. However, its molecular mechanisms remain unclear. Purpose This study investigates the effects of QRHSD on DSS-induced colitis in mice, employing multi-omics analyses, including RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology analysis. Methods The chemical composition of QRHSD was analyzed using quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A UC mice model was induced by 3% DSS for 7 days. The effects and mechanisms of QRHSD on UC were evaluated via hematoxylin and eosin, immunofluorescence assay, flow cytometry, western blot, RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology. Correlation analyses and validation experiments explored links between transcriptomic, microbiome, metabolomic profiles, and UC-related clinical indices. Results UPLC-Q-TOF/MS identified 55 compounds in QRHSD. QRHSD significantly reduced clinical activity, histological changes, and inflammatory factors in UC mice, regulated Th17/Treg balance, and enhanced intestinal barrier integrity. 16S rRNA analysis showed that QRHSD altered gut microbiota composition, increasing beneficial bacteria (e.g., Lactobacillus) and decreasing harmful bacteria (e.g., Morganella). Non-targeted metabolomics revealed 507 metabolites associated with UC amelioration, enriched in pathways like bile secretion, ABC transporters, and amino acid biosynthesis. RNA-seq analysis, network pharmacology, and experimental verification showed that QRHSD significantly regulated key signaling pathways, including PI3K/AKT, NF-κB, and MAPK signaling pathways. Finally, correlation analysis highlighted connections among UC-related clinical factors, gut microbiota, and metabolites. Conclusion QRHSD could modulate the gut microbiota, metabolic homeostasis, and multiple signal pathways in the treatment of DSS-induced UC, revealing the mechanism of traditional Chinese medicine therapy for UC.
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Affiliation(s)
- Wei Chen
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lin Xu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Long Wang
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-nan Shan
- School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Yan Li
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jin-shui Zhu
- Department of Gastroenterology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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18
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Ahn JS, Kim S, Han EJ, Hong ST, Chung HJ. Increasing spatial working memory in mice with Akkermansia muciniphila. Commun Biol 2025; 8:546. [PMID: 40175647 PMCID: PMC11965532 DOI: 10.1038/s42003-025-07975-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 03/20/2025] [Indexed: 04/04/2025] Open
Abstract
Recent research has shown the gut microbiome's impact on memory, yet limitations hinder the identification of specific microbes linked to cognitive function. We measured spatial working memory in individual mice before and after fecal microbiota transplantation (FMT) to develop a targeted analysis that identifies memory-associated strains while minimizing host genetic effects. Transplantation of human fecal into C57BL/6 mice yielded varied outcomes: some mice showed significant improvements while others had negligible changes, indicating that these changes are due to differences in FMT colonization. Metagenomic analysis, stratified by memory performance, revealed a positive correlation between the abundance of Akkermansia muciniphila and improved memory. Moreover, administering two A. muciniphila strains, GMB 0476 and GMB 2066, to wild-type mice elevated spatial working memory via BDNF activation. Our findings indicate that specific gut microbes, particularly A. muciniphila, may modulate memory and represent potential targets for therapeutic intervention in cognitive enhancement.
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Affiliation(s)
- Ji-Seon Ahn
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea
| | - Sura Kim
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk, 54907, Republic of Korea
| | - Eui-Jeong Han
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea
| | - Seong-Tshool Hong
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk, 54907, Republic of Korea.
| | - Hea-Jong Chung
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea.
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
- Department of Bio-Analysis Science, University of Science & Technology, Daejeon, 34113, Republic of Korea.
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19
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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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20
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Xie Q, Liu J, Yu P, Qiu T, Jiang S, Yu R. Unlocking the power of probiotics, postbiotics: targeting apoptosis for the treatment and prevention of digestive diseases. Front Nutr 2025; 12:1570268. [PMID: 40230717 PMCID: PMC11994438 DOI: 10.3389/fnut.2025.1570268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 03/17/2025] [Indexed: 04/16/2025] Open
Abstract
Digestive diseases are becoming an increasingly serious health burden, creating an urgent need to develop more effective treatment strategies. Probiotics and postbiotics have been extensively studied for their potential to prevent and treat digestive diseases. Growing evidence suggests that programmed cell death, especially apoptosis, is a critical mechanism influencing the molecular and biological aspects of digestive diseases, contributing to disease progression. Understanding the mechanisms and signaling pathways by which probiotics and postbiotics regulate apoptosis could reveal new therapeutic targets for treating digestive diseases. This review focuses on the beneficial effects of probiotics and postbiotics in regulating apoptosis across a range of liver diseases, including non-alcoholic fatty liver disease, liver injury, cirrhosis, and liver cancer. It also explores their effects on gastrointestinal diseases, such as colorectal cancer, colitis, gastrointestinal injury, and infectious diarrhea. Furthermore, some probiotics help balance the gut microbiota, enhance intestinal barrier function, and regulate the immune system, all of which are closely associated with apoptosis. Moreover, emerging technologies, such as encapsulation methods, have been developed to stabilize probiotics, primarily based on experimental findings from rodent and human studies.
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Affiliation(s)
- Qiuyan Xie
- Department of Neonatology, Affiliated Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, China
| | - Ji Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Ping Yu
- Reproductive Medicine Centre, Affiliated Women’s Hospital of Jiangnan University, Wuxi, China
| | - Ting Qiu
- Department of Child Health Care, Affiliated Women’s Hospital of Jiangnan University, Wuxi, China
| | - Shanyu Jiang
- Department of Neonatology, Affiliated Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, China
| | - Renqiang Yu
- Department of Neonatology, Affiliated Women’s Hospital of Jiangnan University, Wuxi Maternity and Child Health Care Hospital, Wuxi, China
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21
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Muro P, Jing C, Zhao Z, Jin T, Mao F. The emerging role of honeysuckle flower in inflammatory bowel disease. Front Nutr 2025; 12:1525675. [PMID: 40225345 PMCID: PMC11985448 DOI: 10.3389/fnut.2025.1525675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 03/13/2025] [Indexed: 04/15/2025] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC), referred to as inflammatory bowel disease (IBD), pose considerable challenges in treatment because they are chronic conditions that easily relapse. The occurrence of IBD continues to rise in developing countries. Nonetheless, the existing therapies for IBD have limitations and fail to address the needs of the patients thoroughly. There is an increasing need for new, safe, and highly effective alternative medications for IBD patients. Traditional Chinese Medicine (TCM) is employed in drug development and disease management due to its wide-range of biological activities, minimal toxicity, and limited side effects. Extensive research has shown that certain TCM exhibits significant therapeutic benefits for IBD treatments. Honeysuckle (Lonicera japonica) was used in TCM research and clinical settings for the treatment of IBD. Bioactive metabolites in L. japonica, such as luteolin, quercetin, cyanidin, chlorogenic acid (CGA), caffeic acid (CA), and saponin, exhibit significant therapeutic benefits for managing IBD. The honeysuckle flower is a potential candidate in the treatment of IBD due to its anti-inflammatory, immune system-regulating, and antioxidant qualities. This paper reviews the metabolites of the honeysuckle flower as a candidate for the treatment of IBD. It discusses the fundamental mechanism of L. japonica and the potential of its bioactive metabolites in the prevention and treatment of IBD.
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Affiliation(s)
- Peter Muro
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Caihong Jing
- The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, Jiangsu, China
| | - Zhihan Zhao
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Tao Jin
- Department of Gastrointestinal and Endoscopy, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Fei Mao
- Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
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22
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Liu CQ, Yang J, Ren HF, Liao GN, Yin Z, Gao SL, Du QJ, Yuan XZ, Ullah H, Li K. Diversity of intestinal microbiota and inflammatory cytokines after severe trauma. Sci Rep 2025; 15:7955. [PMID: 40055423 PMCID: PMC11889259 DOI: 10.1038/s41598-025-92212-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/26/2025] [Indexed: 03/17/2025] Open
Abstract
Accumulating evidence has reported that the intestinal microbiota could play important roles in the occurrence and progression of severe trauma. However, the hypothesized potential targeted intestinal microbiota to mediate and regulate the levels of inflammatory cytokines and promote rapid recovery of body after severe trauma remains unclear. This study was aimed to explore the changes and correlation of intestinal microbiota and inflammatory cytokines in rats with severe crush and fracture trauma. The controlled laboratory study design was used, and a crush and fracture severe trauma rat model was established. 16S rRNA high-throughput gene sequencing and ELISA were used to analyze the changes in intestinal microbiota and inflammatory cytokines within one week after trauma. The correlation between intestinal microbiota and inflammatory cytokines was also analyzed. Loss of overall diversity and expansion of intestinal microbiota in the rats due to severe trauma was observed. Specifically, there was a significant increase in the abundance of Muribaculaceae [LDA (Linear Discriminant Analysis)-value = 4.814, P = 0.014] after severe trauma, while Prevotella (LDA-value = 5.235, P = 0.020) and Alloprevotella (LDA-value = 4.443, P = 0.015) were slightly lower in the trauma group than in the control group. The levels of inflammatory cytokines (IL-1α, IL-6, IL-8 and TNF-α) in the trauma group decreased from the first day to the third day and continued to increase until one week after the trauma. Prevotellaceae_UCG_001 was correlated with TNF-a (R = 0.411, P = 0.033); Lactobacillus was negatively correlated with IL-6 (R = - 0.434, P = 0.024) and IL-1α (R = - 0.419, P = 0.030) and positively correlated with IL-8 (R = 0.391, P = 0.045); and Lachnospiraceae_NK4A136_group (R = - 0.559, P = 0.027) and Muribaculaceae (R = - 0.568, P = 0.024) were negatively correlated with IL-8. Severe trauma shows stress-like activities by negatively modulating intestinal microbiota and affecting certain inflammatory cytokines contributing to host health, which implies that the regulation of potentially targeted intestinal microbiota, and further mediating and maintaining the homeostasis of inflammatory cytokines, is expected to promote the accelerating recovery of the body after severe trauma.
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Affiliation(s)
- Chang-Qing Liu
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Jie Yang
- Department of Colorectal Tumour Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Hong-Fei Ren
- Department of Gastroenterology of West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Guang-Neng Liao
- Animal Experiment Center of West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Zhe Yin
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Shi-Lin Gao
- Department of Colorectal Tumour Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Qiu-Jing Du
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Xing-Zhu Yuan
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Hanif Ullah
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
| | - Ka Li
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
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Chu MKW, Day AS, Broad L, Costello SP, Edwards S, Bryant RV. Meta-Analysis: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis. Aliment Pharmacol Ther 2025; 61:756-775. [PMID: 39817370 PMCID: PMC11825926 DOI: 10.1111/apt.18495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 10/15/2024] [Accepted: 12/31/2024] [Indexed: 01/18/2025]
Abstract
BACKGROUND Exclusive enteral nutrition (EEN) is an established dietary therapy for Crohn's disease but its role in ulcerative colitis remains unclear. AIMS To investigate the efficacy of EEN in adults with active ulcerative colitis and compare variations in treatment protocols, safety, tolerability and adherence. METHODS We conducted a systematic search of MEDLINE, Embase, Cochrane CENTRAL, Emcare, CINAHL, Web of Science and trial registries for articles published from inception until July 21, 2024. We included all experimental and observational studies that described the use of EEN in adults with active ulcerative colitis. This review was registered on PROSPERO (CRD42022319584). RESULTS Of 3273 articles screened, we included 10 studies (334 adults). Overall, there was no difference between EEN and comparator for ulcerative colitis remission induction (median follow-up 14 days, risk ratio (RR) 1.15, 95% confidence interval (CI) 0.71-1.85; 2 studies). In acute severe ulcerative colitis, there was no difference between EEN and comparator for corticosteroid failure (RR 0.76, 95% CI 0.48-1.20; 2 studies) or risk of colectomy (RR 0.88, 95% CI 0.51-1.51, n = 2 studies) during index admission. The pooled discontinuation rate was 3% (95% CI 0-10; 9 studies). There was heterogeneity in trial design, methodology and assessment of outcomes. CONCLUSION EEN was well tolerated with low therapy discontinuation in adults with active ulcerative colitis. However, there is insufficient evidence to support the use of EEN as an adjunctive therapy to standard of care. Further, well-designed studies with reproducible methodology and endpoints are necessary to evaluate its effectiveness. REGISTRY NUMBER FOR SYSTEMATIC REVIEW PROSPERO 2022 CRD42022319584.
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Affiliation(s)
- Matthew K. W. Chu
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
| | - Alice S. Day
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
- Nutrition & Dietetics DepartmentCentral Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Lani Broad
- Nutrition & Dietetics DepartmentCentral Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Samuel P. Costello
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
| | - Suzanne Edwards
- School of Public HealthThe University of AdelaideAdelaideSouth AustraliaAustralia
| | - Robert V. Bryant
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
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Futakuchi T, Furuhashi H, Isshi K, Hara Y, Ono S, Kurokawa R, Takayasu L, Suda W, Sumiyama K. Ex Vivo Analysis of the Effect of Endoscopic Premedications on the Microbiota Profile in Gastric Juice. JGH Open 2025; 9:e70141. [PMID: 40114860 PMCID: PMC11924131 DOI: 10.1002/jgh3.70141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 03/06/2025] [Accepted: 03/09/2025] [Indexed: 03/22/2025]
Abstract
Background and Aim Dimethicone (GAS), lidocaine (XYL), and protease (PRO) are commonly used as premedications during esophagogastroduodenoscopy (EGD). However, the effects of these drugs on the gastric microbiota remain unexplored. Therefore, we aimed to investigate the effects of these premedications on gastric juice collected from patients undergoing EGD. Methods Gastric juice was endoscopically aspirated from six patients and divided into six aliquots for in vitro analysis. The samples were mixed with premedications in corresponding treatment sets: GAS, XYL, PRO, MIX (a mixture of GAS, XYL, and PRO), and control (CTL1 and 2; no medication treatment). After extraction of microbial DNA from the treated samples, the 16S rRNA amplicon sequence was analyzed to determine the microbiota profile in terms of (1) the amount of genomic DNA (gDNA), (2) α-diversity indices, Shannon index, number of observed operational taxonomic units (OTUs), and Chao1 index, (3) weighted and unweighted UniFrac distances, and (4) the relative abundance of phyla and genera. Results The total amount of extracted gDNA did not significantly differ between the six groups. The α-diversity indices did not significantly differ between treatment groups. Although GAS, PRO, and MIX differed significantly from the technical replicates in the weighted UniFrac distance (p = 0.03 all), no significant difference was observed in the unweighted UniFrac distance. However, significant differences were observed in the relative abundance of several bacterial microbiota at the phylum and genus levels. Conclusions Premedications affect the microbiota profile of specific phylum- and genus-level bacterial groups. Trial Registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN-CTR 000040192 and UMIN-CTR 000051289.
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Affiliation(s)
- Toshiki Futakuchi
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Hiroto Furuhashi
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Kimio Isshi
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
- Isshi Gastro-Intestinal Clinic Tokyo Japan
| | - Yuko Hara
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Shingo Ono
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Rina Kurokawa
- Laboratory for Symbiotic Microbiome Sciences RIKEN Center for Integrative Medical Sciences Kanagawa Japan
| | - Lena Takayasu
- Laboratory for Symbiotic Microbiome Sciences RIKEN Center for Integrative Medical Sciences Kanagawa Japan
| | - Wataru Suda
- Laboratory for Symbiotic Microbiome Sciences RIKEN Center for Integrative Medical Sciences Kanagawa Japan
| | - Kazuki Sumiyama
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
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25
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Yang Q, Kang Y, Tang W, Li M, Zhao C. Interplay of gut microbiota in Kawasaki disease: role of gut microbiota and potential treatment strategies. Future Microbiol 2025; 20:357-369. [PMID: 40013895 PMCID: PMC11938985 DOI: 10.1080/17460913.2025.2469432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
Kawasaki disease (KD) is an acute systemic immune vasculitis with predominant involvement of the medium and small arteries. It mostly affects pediatric patients, representing the most common form of pediatric vasculitis in children less than 5 years old. Numerous diseases, especially those related to the immune system, have established links with the intestinal flora. Recent studies have investigated the intestinal flora changes throughout the management of KD. There was gut microbiota dysbiosis in pediatric KD at the acute phase, particularly the downregulation of short-chain fat acids-producing microbiota and the over-proliferation of opportunistic pathogens. The relationship between the response to therapies in individuals with KD and specific microbiota remains uncertain. Targeted microbial supplements and dietary regulation may serve as potential measures to alleviate KD complications and thus improve prognosis. This review provides an overview of the current understanding of the interplay of the gut microbiota and KD. Furthermore, it discusses the possibility of altering the gut microbiota to reinstate a healthy condition.
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Affiliation(s)
- Qing Yang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Yaqing Kang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Wei Tang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Meng Li
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Cuifen Zhao
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
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Sandu R, Singh J. A comprehensive review on calcitonin gene-related peptide in the management of gastrointestinal disorders. Inflammopharmacology 2025; 33:1043-1059. [PMID: 39934537 DOI: 10.1007/s10787-025-01657-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025]
Abstract
The prevalence of gastrointestinal disorders caused by alcohol, Helicobacter pylori, non-steroidal anti-inflammatory drugs, chronic stress and sedentary lifestyle is on the rise. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, has emerged as a protective factor against various gastrointestinal issues. Despite its known benefits, the dual role of CGRP in gastrointestinal damage remains unclear. Discovered 30 years ago through alternative RNA processing of the calcitonin gene, CGRP is known to be a potent vasodilator involved in crucial defensive mechanisms for both physiological and pathological conditions. Promising evidences from preclinical research have attracted the interest of scientists for the exploration of CGRP as a therapeutic neuropeptide. Numerous evidences suggest that this neuropeptide is secreted by the neurons under the influence of endogenous as well as exogenous stimuli. CGRP repairs the gastric mucosal barrier and maintain mucosal integrity by suppressing NF-κB activation, thereby reducing tumour necrosis factor-alpha expression. In addition, recent studies suggest that CGRP modulates immune responses and enhances epithelial cell proliferation, further contributing to its cytoprotective effects. Consequently, CGRP and the CGRP secretagogues represent promising novel targets for clinical applications. This review aims to elucidate the role of CGRP and CGRP secretagogues in the management of gastrointestinal disorders, highlighting its potential as a therapeutic agent in the context of evidence-based modern gastroenterology.
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Affiliation(s)
- Rajesh Sandu
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, 160062, Punjab, India
| | - Jagtar Singh
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, 160062, Punjab, India.
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Zheng X, Fan J, Yin J, Chu Y. The role of gut microbiota and plasma metabolites in ulcerative colitis: Insights from Mendelian randomization analysis. Medicine (Baltimore) 2025; 104:e41710. [PMID: 40020117 PMCID: PMC11875619 DOI: 10.1097/md.0000000000041710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 02/11/2025] [Indexed: 03/05/2025] Open
Abstract
Emerging research suggests that alterations in gut microbiota composition may play a significant role in the pathogenesis of ulcerative colitis (UC). Plasma metabolites, which are influenced by gut microbiota, have also been implicated, but their role in UC remains unclear. This study aims to determine whether specific plasma metabolites mediate the causal relationship between gut microbiota and UC using Mendelian randomization (MR) analysis. This study employed publicly available summary-level data from genome-wide association studies and metagenomic datasets. Gut microbiota data were derived from the FINRISK cohort (5959 participants), plasma metabolite data from the Canadian Longitudinal Study on Aging (8299 individuals), and UC data from multiple consortia (17,030 cases and 883,787 controls). Forward and reverse MR analyses, supplemented by linkage disequilibrium score regression (LDSC), were conducted to assess causal relationships. Mediation effects of plasma metabolites between gut microbiota and UC were analyzed using the product of coefficients method. Various sensitivity analyses, including MR-Egger and MR-PRESSO, were applied to detect pleiotropy and ensure robust results. The study identified 20 bacterial taxa and 93 plasma metabolites linked to UC. Forward MR analysis showed that Clostridium S felsineum increased UC risk via reduced carnitine levels, with a mediation proportion of 39.77%. Eubacterium callanderi was associated with decreased UC risk through the tryptophan to pyruvate ratio (16.02% mediation). Additionally, species CAG-590 sp000431135 increased UC risk through elevated mannitol/sorbitol levels, mediating 28.38% of the effect. Sensitivity analyses confirmed the robustness of these findings, with minimal heterogeneity and pleiotropy detected. This study highlights the significant role of gut microbiota and their associated plasma metabolites in the pathogenesis of UC. Specific microbial species influence UC through metabolites, suggesting potential therapeutic targets. Modulating carnitine, tryptophan metabolism, or sugar alcohols could offer promising avenues for UC management.
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Affiliation(s)
- XuWen Zheng
- Emergency Department, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China
| | - JinNuo Fan
- Emergency Department, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China
| | - JinNan Yin
- Emergency Department, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China
| | - Ying Chu
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
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Chen H, Yuan J, Zhou H, Zhan X, Gao Y, Chen B, Aihemaiti N, Xu X, Dong Y, Liu S, Chen Y, Liu D, Xie T, Xu Y. Characterization of the gut microbiota in urinary calculi patients with preoperative urinary tract infection. Front Cell Infect Microbiol 2025; 15:1417403. [PMID: 40093533 PMCID: PMC11906712 DOI: 10.3389/fcimb.2025.1417403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 02/03/2025] [Indexed: 03/19/2025] Open
Abstract
Background Urinary tract infection is one of the most common comorbidities of urinary stones. Disorders of gut microbiota can affect various infectious diseases and the formation of the stones. Therefore, alterations in the gut bacteria profile may be a potential risk factor for the development of infections in patients with urinary tract stones. Methods We conducted a retrospective study to analyze the association of urinary tract infections with gut microbiota and serum metabolism in patients with stones. Results Patients with urolithiasis were predominantly in combination with diabetes mellitus (11.4% vs. 20%) and hypertension (36.4% vs. 50%). There were no statistically significant differences in hematological and urinary parameters. Compared to negative patients, IL-17A was significantly higher in the positive group (25.0 vs 21.1 pg/ml p = 0.038). The majority of pathogens detected in urine cultures were urease-negative bacteria, and urease-positive bacteria accounted for 15% of the total number of patients. We analyzed the community composition of the two groups of patients and found a significant difference in their β-diversity (p = 0.025), suggesting that dysbiosis of the gut bacteria may be associated with the combination of urinary tract infections in urolithiasis. For identification of crucial bacteria, we found changes in the abundance of both Intestinibacter (p = 0.036) and Dialister (p = 0.039), and abundance of Intestinibacter was positively correlated with IFN-α, IL-12P70 (p<0.05), and especially IL-17A (p<0.01), which may result from differences in translational, ribosomal structural and biosynthetic functions in stone patients (p < 0.05). Conclusion Urolithiasis with gut dysbiosis developed a higher incidence of urinary tract infections, which may be associated with the increasing of Intestinibacter and affect the expression of IL-17A by translational, ribosomal structural and biosynthetic function.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Tiancheng Xie
- Department of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yunfei Xu
- Department of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
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Yang CC, Zhang S, Zhang R, Zhao YN, Yang DW, Yang MY, Huang LJ. Application of Saccharomyces boulardii in combination with sulfasalazine in ulcerative colitis patients demonstrates significant effectiveness. World J Gastrointest Surg 2025; 17:102342. [DOI: 10.4240/wjgs.v17.i2.102342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/07/2024] [Accepted: 12/26/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a complex inflammatory bowel disease, and its etiology and pathogenesis remain incompletely elucidated.
AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.
METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted. All patients met complete inclusion and exclusion criteria. Based on the treatment interventions received, they were divided into a control group (n = 63) and an observation group (n = 64). Both groups of patients received routine treatment upon admission. The control group received sulfasalazine in addition to routine interventions, while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment. The clinical efficacy, improvement in symptoms, modified Baron endoscopic scores, quality of life “inflammatory bowel disease questionnaire (IBDQ)”, levels of intestinal microbial indicators (such as Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli), intestinal mucosal barrier function indicators [diamine oxidase (DAO), lipopolysaccharide (LPS), D-lactic acid (D-LA)], and adverse reaction occurrences were compared between the two groups.
RESULTS (1) Clinical efficacy: The total effective rate in the control group was 79.37%, while in the observation group, it was 93.75%, significantly higher than that of the control group (P < 0.05); (2) Improvement in symptoms: The observation group showed significantly lower relief time for abdominal pain, diarrhea, rectal bleeding, fever symptoms, and mucosal healing time compared to the control group (P < 0.05); (3) Baron endoscopic scores and IBDQ scores: Before treatment, there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups (P > 0.05). However, after treatment, the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group (P < 0.05); (4) Levels of intestinal microbial indicators: Before treatment, there was no significant difference in the levels of Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli between the two groups (P > 0.05). After treatment, the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group, while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group (P < 0.05); (5) Levels of intestinal mucosal barrier function indicators: Before treatment, there was no significant difference in the levels of DAO, LPS, and D-LA between the two groups (P > 0.05). However, after treatment, the levels of DAO, LPS, and D-LA in the observation group were significantly lower than those in the control group (P < 0.05); and (6) Occurrence of adverse reactions: The incidence of adverse reactions in the control group was 9.52%, while in the observation group, it was 10.94%. There was no significant difference in the occurrence of adverse reactions between the two groups (P > 0.05).
CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness. Compared to sole sulfasalazine intervention, the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients, alleviates intestinal mucosal inflammation, and improves the quality of life. Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function. Moreover, the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients, indicating a higher level of medication safety and advocating for its clinical promotion and application.
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Affiliation(s)
- Chun-Chun Yang
- Department of Gastroenterology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Sui Zhang
- Department of Hepatic, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Rui Zhang
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Ya-Nan Zhao
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Da-Wei Yang
- Department of Hepatic, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Ming-Yue Yang
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Li-Jing Huang
- Department of Rheumatology and Immunology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
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Li Y, Li B, Gou Y, Tian X, Chang L, Qu C. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis. Open Med (Wars) 2025; 20:20241126. [PMID: 40028263 PMCID: PMC11868706 DOI: 10.1515/med-2024-1126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 03/05/2025] Open
Abstract
Objective The purpose of this article was to unravel the clinical efficacy of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in the treatment of mild-to-moderate ulcerative colitis (UC). Methods Eighty-six mild-to-moderate UC patients were selected as study subjects and randomized into the control group (treated with mesalazine enteric-coated tablets [Salofalk]) and the observation group (treated with mesalazine enteric-coated tablets, Bifidobacterium Tetravaccine Tablets, and Yiyi Baitouweng Decoction retention enema). The clinical efficacy, colonoscopy score, serum levels of inflammatory factors, and the incidence of adverse reactions were compared. Results The clinical efficacy of patients in the observation group was better in contrast to the control group. After 8 weeks of treatment, the colonoscopy score, and levels of TNF-α, IFN-γ, CRP, and ESR were lower, while IL-10 levels were higher in patients of both groups than those before treatment; lower colonoscopy score and levels of TNF-α, IFN-γ, CRP, and ESR and higher IL-10 levels were observed in the observation group versus the control group. Conclusion Probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema have remarkable clinical effects in treating mild-to-moderate UC.
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Affiliation(s)
- Yanlong Li
- Diagnosis and Treatment Center for Spleen and Stomach Diseases, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou730030, Gansu, China
| | - Baoyu Li
- College of Integrated Chinese and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou730000, Gansu, China
| | - Yuqin Gou
- College of Integrated Chinese and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou730000, Gansu, China
| | - Xudong Tian
- Diagnosis and Treatment Center for Spleen and Stomach Diseases, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou730030, Gansu, China
| | - Lijun Chang
- Chronic Non communicable Disease Control Institute, Gansu Provincial Center for Disease Control and Prevention, Lanzhou730000, Gansu, China
| | - Chaoxu Qu
- Endocrinology Department of Spleen and Stomach Diseases, Xigu District Traditional Chinese Medicine Hospital, Lanzhou730060, Gansu, China
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Garfias Noguez C, Ramírez Damián M, Ortiz Moreno A, Márquez Flores YK, Alamilla Beltrán L, Márquez Lemus M, Bermúdez Humarán LG, Sánchez Pardo ME. Microencapsulation and Probiotic Characterization of Lactiplantibacillus plantarum LM-20: Therapeutic Application in a Murine Model of Ulcerative Colitis. Nutrients 2025; 17:749. [PMID: 40077619 PMCID: PMC11901509 DOI: 10.3390/nu17050749] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 02/16/2025] [Accepted: 02/18/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Microencapsulation improves the storage, handling, and administration of probiotics by protecting them from environmental factors and adverse conditions in the gastrointestinal tract. This process facilitates their controlled delivery in the body, which can simplify their use in therapies without compromising their therapeutic efficacy. OBJECTIVES This study investigates the microencapsulation of Lactiplantibacillus plantarum LM-20, its probiotic properties, and its effects in a murine model of ulcerative colitis. METHODS/RESULTS Synbiotic microencapsulation was carried out using spray drying with maltodextrin, gum Arabic, and inulin, achieving an encapsulation efficiency of 90.76%. The resulting microcapsules exhibited remarkable resistance to simulated gastrointestinal conditions in vitro, maintaining a survival rate of 90%. The drying process did not compromise the probiotic characteristics of the bacteria, as they demonstrated enhanced auto-aggregation, hydrophobicity, and phenol tolerance. The therapeutic potential of the microencapsulated synbiotic was evaluated in a murine model of dextran sodium sulfate-induced ulcerative colitis. The results revealed that mice treated with microencapsulated Lactiplantibacillus plantarum LM-20 showed an 83.3% reduction in the disease activity index (DAI) compared to the ulcerative colitis control group. Moreover, a significant decrease was observed in pro-inflammatory cytokine levels (IL-1β and TNF-α) and myeloperoxidase activity, with values comparable to those of the healthy control group. CONCLUSIONS These findings suggest that microencapsulated Lactiplantibacillus plantarum LM-20 could be a promising candidate for therapeutic applications in the prevention and management of ulcerative colitis.
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Affiliation(s)
- Cynthia Garfias Noguez
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Morayma Ramírez Damián
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Alicia Ortiz Moreno
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Yazmín Karina Márquez Flores
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Liliana Alamilla Beltrán
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Mario Márquez Lemus
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Luis G. Bermúdez Humarán
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Domain de Vilvert, 78350 Jouy-en-Josas, France;
| | - María Elena Sánchez Pardo
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
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Chen L, Xie L, Wang L, Zhan X, Zhuo Z, Jiang S, Miao L, Zhang X, Zheng W, Liu TM, He J, Liu Y. Patchoulene epoxide mitigates colitis and hepatic damage induced by dextran sulfate sodium by regulating the colonic microbiota and purine metabolism. Front Immunol 2025; 16:1509114. [PMID: 40028318 PMCID: PMC11868103 DOI: 10.3389/fimmu.2025.1509114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 01/29/2025] [Indexed: 03/05/2025] Open
Abstract
Introduction Ulcerative colitis (UC) is often characterized by dysbiosis of the colonic microbiota and metabolic disturbances, which can lead to liver damage. Patchoulene epoxide (PAO), a tricyclic sesquiterpene derived from the aged essential oil of Pogostemonis Herba, is known for its anti-inflammatory and ulcer-healing properties. However, its dual protective role against UC and liver injury remains largely unexplored. This study aims to elucidate the protective effect and underlying mechanism of PAO against dextran sulfate sodium (DSS)-induced UC and liver injury in mice. Methods Colitis and liver injury in mice were induced by adding 3% DSS to their drinking water continuously for 7 days, and PAO at the doses of 20 and 40 mg/kg was administered orally to mice daily from the first day until the experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon and liver tissues were collected for biochemical analyses. Additionally, the fecal microbiome and its metabolites of treated mice were characterized using 16S rRNA amplicon sequencing and metabolomics. Results PAO significantly reduced the disease activity index and mitigated colonic atrophy in UC mice. It also improved colonic and hepatic pathological changes by safeguarding tight and adherens junctions, and suppressing the generation of pro-inflammatory cytokines and lipopolysaccharide. These beneficial effects were attributed to PAO's capability to regulate the colonic microbiota and metabolic processes. PAO was found to enhance the diversity of the colonic microbiota and to shift the microbial balance in UC mice. Specifically, it restored the microbiota from an Akkermansia-dominated state, characteristic of UC, to a healthier Muribaculaceae-dominated composition. Furthermore, PAO corrected the colon metabolic disturbance in UC mice by modulating the purine metabolism, notably increasing the abundance of deoxyadenosine, adenosine and guanine in UC mice. Conclusions The therapeutic effect of PAO on UC and liver injury was mainly attributed to its regulation of colonic microbiota and purine metabolism. These insights emphasize the overall therapeutic benefits of PAO in treating UC and liver injury.
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Affiliation(s)
- Liping Chen
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lili Xie
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lifen Wang
- Cancer Center, Faculty of Health Sciences, University of Macau, Macau, Macao SAR, China
| | - Xueli Zhan
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhenjian Zhuo
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- Laboratory Animal Center, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China
| | - Susu Jiang
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lei Miao
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xinxin Zhang
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Weiming Zheng
- Institute of Translational Medicine, Faculty of Health Sciences & Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, China
| | - Tzu-Ming Liu
- Institute of Translational Medicine, Faculty of Health Sciences & Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, China
| | - Jing He
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yuhong Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
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Jin Y, Liu H, Wang Y, Zhang R, Wang Q, Wang Y, Cui H, Wang X, Bian Y. Pathogenesis and treatment of colitis-associated colorectal cancer: Insights from Traditional Chinese Medicine. JOURNAL OF ETHNOPHARMACOLOGY 2025; 338:119096. [PMID: 39532222 DOI: 10.1016/j.jep.2024.119096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 10/11/2024] [Accepted: 11/09/2024] [Indexed: 11/16/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Inflammatory Bowel Disease (IBD) is an inflammatory intestinal disease, and with prolonged illness duration, the annual risk of IBD progressing to colitis-associated colorectal cancer (CAC) gradually increases. In recent years, there has been a noticeable trend towards the application of traditional Chinese medicine (TCM) in the treatment of CAC. AIM OF THIS REVIEW This comprehensive review summarizes the pathogenesis of CAC and details the therapeutic benefits of TCM in treating CAC, including various TCM prescriptions and ingredients, establishing the theoretical foundation for the application of TCM in CAC treatment. METHODS We assessed literature published before March 24, 2024, from several databases, including Web of Science, PubMed, Scopus and Google Scholar. The keywords used include "traditional Chinese medicine", "traditional Chinese medicine prescriptions", "traditional Chinese medicine ingredients", "herbal medicine", "colitis-associated colorectal cancer", "inflammatory bowel disease", "colorectal cancer" and "colitis-cancer transformation". We conducted a comprehensive collection and collation of pertinent scientific articles from various databases, focusing on the efficacy of TCM in the prevention and treatment of "colitis-cancer transformation". RESULTS This paper provides a concise summary and thorough analysis of twenty-eight prescriptions and ingredients of TCM for the prevention and treatment of CAC, based on existing experimental and clinical research. There are positive signs that TCM can effectively prevent and treat the "colitis-cancer transformation" through repairing the intestinal mucosal barrier, correcting intestinal flora imbalance, and regulating intestinal immune responses. CONCLUSION TCM possesses comprehensive regulatory advantages that are multifaceted, multilevel, and multitarget. It has a definite curative effect in the prevention and treatment of CAC. It is essential to enhance the clinical efficacy of TCM in the prevention and treatment of CAC based on syndrome differentiation and treatment, with the assistance of modern medicine.
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Affiliation(s)
- Yutong Jin
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Haizhao Liu
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300192, China
| | - Yuhui Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Ruixuan Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Qiaochu Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300073, China
| | - Yao Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Huantian Cui
- First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China.
| | - Xiangling Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Yuhong Bian
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
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Jiao X, Li Y, Hu Y, Yan R, Fu T, Liu J, Li Z. Antibiotic-Induced dysbiosis of the ocular microbiome affects corneal circadian rhythmic activity in mice. Mucosal Immunol 2025:S1933-0219(25)00010-8. [PMID: 39920996 DOI: 10.1016/j.mucimm.2025.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 01/09/2025] [Accepted: 01/28/2025] [Indexed: 02/10/2025]
Abstract
The ocular surface microbiota plays a critical role in maintaining corneal homeostasis, but its disruption and subsequent effects on corneal functions remain poorly understood. This study investigates how antibiotic-induced microbial depletion affects the corneal circadian transcriptome in C57BL/6J mice. Dysbiosis was induced using a topical antibiotic cocktail, and RNA sequencing was employed to analyze gene expression across eight time points over 24 h. Antibiotic treatment disrupted corneal circadian rhythms, eliminating rhythmicity in 1,812 genes and introducing rhythmicity in 1,928 previously arrhythmic genes. Furthermore, epithelial adhesion was impaired, inflammation was elevated, and neural sensitivity was reduced. More than 50 % of ocular microbial genera exhibited daily oscillations, with six genera showing significant correlations with corneal rhythmic transcripts. Additionally, the administration of TLR agonists restored circadian gene expression patterns, with partial recovery of corneal barrier function and immune homeostasis, further highlighting the potential of microbiota-targeted therapies in treating ocular surface disorders. These findings underscore the critical role of the ocular microbiota in regulating corneal health and suggest that restoring microbial balance via TLR activation may offer new therapeutic avenues for eye diseases.
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Affiliation(s)
- Xinwei Jiao
- Department of Pathology, Medical School, Jinan University, Guangzhou, China; International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China
| | - Yan Li
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yu Hu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ruyu Yan
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ting Fu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jun Liu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Zhijie Li
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
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Kucharski R, Sobocki BK, Stachowska E, Bulman N, Kalinowski L, Kaźmierczak-Siedlecka K. Dental problems and oral microbiome alterations in ulcerative colitis. Front Immunol 2025; 16:1502605. [PMID: 39975550 PMCID: PMC11836005 DOI: 10.3389/fimmu.2025.1502605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 01/13/2025] [Indexed: 02/21/2025] Open
Abstract
Ulcerative colitis is a chronic disease that has not well-established etiology. The role of microbial dysregulation in its pathogenesis has been recently highlighted. Overall, microbiome alterations concern the reduction of bacterial abundance and diversity, resulting in gut microbiome imbalance negatively affecting immunological aspects. There is a link between ulcerative colitis and the oral microbiome. The changes of oral microbiome are found at many levels, from gently dysbiotic composition to the presence of the main periodontal microbes. The analysis of oral microbiome can be a part of personalized medicine due to the fact that it is a potential biomarker. Patients with ulcerative colitis may manifest dental symptoms/problems, such as periodontitis (strongly related to the red-complex pathogens-Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and bacteria belonging to the other complexes, such as Fusobacterium nucleatum and Aggregatibacter actinomycetecomitans), dental caries, oral ulcerations, leukoplakia, halitosis, and others. Notably, the DMFT (Decayed, Missing, Filled Teeth) index is higher in these patients compared to healthy subjects. According to some data, oral lichen planus (which is a disease with an immunological background) can also be observed in ulcerative colitis patients. It seems that deep understanding of ulcerative colitis in association with oral microbiome, immunology, and dental manifestations may be crucial to provide complex treatment from a dental point of view.
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Affiliation(s)
- Robert Kucharski
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
- Neodentica Dentistry Center, Gdansk, Poland
| | - Bartosz Kamil Sobocki
- Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdańsk, Poland
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Nikola Bulman
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
| | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
- BioTechMed Center, Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gdansk, Poland
| | - Karolina Kaźmierczak-Siedlecka
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
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Mousavi SN, Momeni N, Chiti H, Mahmoodnasab H, Ahmadi M, Heidarzadeh S. Higher gut Bacteroidetes and Actinobacteria population in early pregnancy is associated with lower risk of gestational diabetes in the second trimester. BMC Pregnancy Childbirth 2025; 25:106. [PMID: 39901086 PMCID: PMC11789361 DOI: 10.1186/s12884-025-07192-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 01/16/2025] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Despite the association between the gut dysbiosis and metabolic disorders, the main bacterial phylum in the first trimester of pregnancy that predisposes mothers to gestational diabetes mellitus (GDM) in the second trimester is not clear around the world. MATERIALS AND METHODS Three-hundred healthy women aged 18-40 years who were in the first trimester were participated in this cohort study and followed to the screening time for GDM diagnosis (in 24-28 weeks of pregnancy). Stool samples were gathered in the first trimester. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Groups. In total, thirty mothers were diagnosed with GDM. Controls (N = 60) were selected from non-GDM participants matching to the GDM in terms of pre-pregnancy weight, weight gain, dietary intake and familial history of diabetes. The dominant phylum population was determined based on 16SrRNA gene expression. RESULTS Mothers with lower Bacteroidetes and Actinobacteria population in the first trimester were more susceptible to GDM in the screening time (p < 0.001 and p < 0.001). The Firmicutes to Bacteroidetes ratio was significantly higher in mothers with GDM than the controls (p < 0.001). A significant negative correlation was observed between the gut Bacteroidetes (p < 0.001, p < 0.001, p < 0.001) and Actinobacteria (p = 0.004, p < 0.001, p = 0.02) population in the first trimester with the the serum FBS, 1 h-PG and 2 h-PG levels in the screening time. However, the gut Firmicutes to Bacteroidetes ratio (p = 0.003, p = 0.01) showed a significant positive correlation with serum FBS and 1 h-PG levels. CONCLUSIONS A higher Bacteroidetes and Actinobacteria population in the gut of mothers at the first trimester was associated with lower risk of GDM in the screening time. Higher Firmicutes to Bacteroidetes ratio in the gut of mothers was associated with fasting and 1-h glucose intolerance in the screening time.
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Affiliation(s)
- Seyedeh Neda Mousavi
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute , Zanjan University of Medical Sciences, Zanjan, Iran.
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Navid Momeni
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute , Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Chiti
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute , Zanjan University of Medical Sciences, Zanjan, Iran
| | - Howra Mahmoodnasab
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammad Ahmadi
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Siamak Heidarzadeh
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Ibrahim D, Khater SI, Sherkawy HS, Elgamal A, Hasan AA, Muhammed AA, Farag MFM, Eissa SA, Ismail TA, Eissa HM, Eskandrani AA, Alansari WS, El-Emam MMA. Protective Role of Nano-encapsulated Bifidobacterium breve, Bacilllus coagulans, and Lactobacillus plantarum in Colitis Model: Insights Toward Propagation of Short-Chain Fatty Acids and Reduction of Exaggerated Inflammatory and Oxidative Response. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10472-y. [PMID: 39900879 DOI: 10.1007/s12602-025-10472-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2025] [Indexed: 02/05/2025]
Abstract
Irritable bowel disease (IBD), also known as ulcerative colitis and Crohn's disease, is a chronic inflammatory disorder affecting millions of people worldwide. Herein, nano-encapsulated multi-strain probiotics formulation, comprising Bifidobacterium breve DSM24732 and B. coagulans SANK 70258 and L. plantarum DSM24730 (BBLNPs) is used as an effective intervention technique for attenuating IBD through gut microenvironment regulation. The efficacy of the prophylactic role of BBLNPs in alleviating injury induced by dextran sulfate sodium (DSS) was evaluated by assessing oxidative and inflammatory responses, levels of short-chain fatty acids (SCFAs) and their regulation on GPR41/43 pathway, expression of genes related to tight-junctions and autophagy, immunohistochemistry of IL1β and GPR43, and histological examination of inflamed colonic tissue. The severity of clinical signs and paracellular permeability to FITC (fluorescein isothiocyanate)-labeled dextran was significantly decreased after BBLNP treatment. Reduction of oxidative stress-associated biomarkers (MDA, ROS, and H2O2) and acceleration of antioxidant enzyme activities (SOD, CAT, and GSH-Px) were noted in the BBLNP-treated group. Subsiding of inflammatory markers (TNF-α, IL-18, IL-6, TRL-4, CD-8, NLRP3, and caspase 1) and upregulation of tight-junction-related genes (occludin and JAM) was detected in BBLNPs. Administration of BBLNPs remarkably resulted in a higher level of SCFAs which parrel with colonic upregulation of GPR41 and GPR43 expression compared to DSS-treated rats. Notable modulation of autophagy-related genes (p62, mTOR, LC3, and Beclin-1) was identified post BBLNP treatment. The mRNA expressions of p62 and mTOR were significantly downregulated, while LC3 and Beclin-1 were upregulated after prophylactic treatment with BBLNPs. Immune-stained labeled cells showed lower expression of IL-1β and higher expression levels of GPR43 in BBLNPs compared to the DSS-induced group. The intestinal damage caused by DSSwas effectively mitigated by oral BBLNP treatment, as supported by the restoration of healthy colonic tissue architecture. The findings suggest that BBLNPs have a promising avenue in the remission of IBD by modulating inflammation, oxidative stress, microbial metabolites such as SCFAs, and autophagy.
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Affiliation(s)
- Doaa Ibrahim
- Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.
| | - Safaa I Khater
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt
| | - Hoda S Sherkawy
- Department of Medical Biochemistry, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Aya Elgamal
- Department of Animal Histology and Anatomy, Faculty of Veterinary Medicine, Badr University in Cairo (BUC), Cairo, Egypt
| | - Asmaa A Hasan
- Department of Human Anatomy and Embryology, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Asmaa A Muhammed
- Department of Medical Physiology, Faculty of Medicine, Aswan University, Aswan, 81511, Egypt
| | - Mohamed F M Farag
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Samar A Eissa
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt
| | - Tamer Ahmed Ismail
- Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, 21944, Taif, Saudi Arabia
| | - Hemmat M Eissa
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt
| | - Areej A Eskandrani
- Chemistry Department, College of Science, Taibah University, Medina, Saudi Arabia
| | - Wafa S Alansari
- Biochemistry Department, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia
| | - Mahran Mohamed Abd El-Emam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt
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Lista S, Munafò A, Caraci F, Imbimbo C, Emanuele E, Minoretti P, Pinto-Fraga J, Merino-País M, Crespo-Escobar P, López-Ortiz S, Monteleone G, Imbimbo BP, Santos-Lozano A. Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives. Ageing Res Rev 2025; 104:102659. [PMID: 39800223 DOI: 10.1016/j.arr.2025.102659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/29/2024] [Accepted: 01/09/2025] [Indexed: 01/15/2025]
Abstract
Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.
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Affiliation(s)
- Simone Lista
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Antonio Munafò
- Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence 50139, Italy.
| | - Filippo Caraci
- Department of Drug and Health Sciences, University of Catania, Catania 95125, Italy; Oasi Research Institute-IRCCS, Troina 94018, Italy.
| | - Camillo Imbimbo
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia 27100, Italy.
| | | | | | - José Pinto-Fraga
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - María Merino-País
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Paula Crespo-Escobar
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Susana López-Ortiz
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Unit of Gastroenterology, Policlinico Tor Vergata University Hospital, Rome 00133, Italy.
| | - Bruno P Imbimbo
- Department of Research and Development, Chiesi Farmaceutici, Parma 43122, Italy.
| | - Alejandro Santos-Lozano
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid 28041, Spain.
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Zhao H, Fu X, Wang Y, Shang Z, Li B, Zhou L, Liu Y, Liu D, Yi B. Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation. Mol Nutr Food Res 2025; 69:e202400785. [PMID: 39812000 DOI: 10.1002/mnfr.202400785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/17/2024] [Accepted: 12/20/2024] [Indexed: 01/16/2025]
Abstract
This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.
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Affiliation(s)
- Hu Zhao
- 2nd Abdominal Surgery Department, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
- Jiangxi Cancer Institute, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
- Department of Burns and Surgery, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, People's Republic of China
| | - Xingxing Fu
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Yaru Wang
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Zhao Shang
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - BangHua Li
- Department of Integrated Traditional Chinese and Western Medicine Oncology, and Third Ward of Gastrointestinal Oncology, Nanchang, Jiangxi, People's Republic of China
| | - Li Zhou
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Yue Liu
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Dan Liu
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Bo Yi
- 2nd Abdominal Surgery Department, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
- Jiangxi Cancer Institute, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
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40
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Levy S, Jiang AK, Grant MR, Arp G, Minabou Ndjite G, Jiang X, Hall B. Convergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut. Nat Commun 2025; 16:1121. [PMID: 39875389 PMCID: PMC11775122 DOI: 10.1038/s41467-025-56332-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 01/14/2025] [Indexed: 01/30/2025] Open
Abstract
Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens. A systematic bioinformatic search for the gud/gar pathway in gut microbes identified 887 species putatively capable of metabolizing oxidized sugars. Previous studies showed that inflammation-derived nitrate, formed by nitric oxide reacting with superoxide, promotes pathogen growth. Our findings reveal a parallel phenomenon: oxidized sugars, also produced from reactions with nitric oxide, serve as alternative carbon sources for commensal microbes. Previously considered a pathogen virulence factor, oxidized sugar metabolism is also present in specific commensals and may contribute to their increased relative abundance in gastrointestinal inflammation.
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Affiliation(s)
- Sophia Levy
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Angela K Jiang
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA
- National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
| | - Maggie R Grant
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Gabriela Arp
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Glory Minabou Ndjite
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Xiaofang Jiang
- National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
| | - Brantley Hall
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA.
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA.
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41
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Zhao Y, Liang S, Fu X, Guo Y, Wang Y, Wang J, Wang X, Wang Z, Tao H, Han B, Wang J. Anti-Inflammatory and Antidiarrheal Effects of Two Strains of Lactic Acid Bacteria Isolated from Healthy Pets on Escherichia coli K88-Induced Diarrhea in Mice. Microorganisms 2025; 13:239. [PMID: 40005605 PMCID: PMC11857690 DOI: 10.3390/microorganisms13020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/17/2025] [Accepted: 01/19/2025] [Indexed: 02/27/2025] Open
Abstract
Lactic acid bacteria play a crucial role in maintaining the health of the host's gut microbiota. In this study, the anti-inflammatory properties of Limosilactobacillus reuteri LR20-6 and Lacticplantibacillus plantarum L272 were evaluated using a mouse model of diarrhea induced by Escherichia coli. We also investigated their effects on gut microbiota regulation. The results indicated that both Lacticplantibacillus plantarum and Limosilactobacillus reuteri could reduce inflammation by inhibiting the expression of inflammatory factors IL-6 and TNF-α and blocking the MyD88 and NF-kB/p65 signaling pathways. Additionally, after intervention with these strains, the relative abundance of Lactobacillus was significantly increased. This suggested that Lacticplantibacillus plantarum and Limosilactobacillus reuteri could mitigate the severity of E. coli-induced diarrhea and enhance the abundance of beneficial probiotics in the gut of animals.
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Affiliation(s)
- Ya Zhao
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Shukun Liang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Xiaoxin Fu
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Yaping Guo
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Yu Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Jiaxue Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Xiumin Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Zhenlong Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Hui Tao
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Bing Han
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Jinquan Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
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Gong S, Yu Z, Ding Y, Wang Y, Li X, Gu S. Characteristics of functional constipation and analysis of intestinal microbiota in children aged 0-4 in Zunyi region. BMC Pediatr 2025; 25:45. [PMID: 39825285 PMCID: PMC11748605 DOI: 10.1186/s12887-024-05383-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 12/30/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Functional constipation (FC) significantly impacts children's health. This study investigates the prevalence and microbiota characteristics of FC in children aged 0-4 years in Zunyi area. METHODS From October to December 2023, 2039 children aged 0-4 years in Zunyi were selected using stratified sampling and cross-sectional survey methods. A questionnaire based on Rome IV diagnostic criteria was used. Twenty-nine children with FC were randomly selected as the functional constipation group (FCG), and 26 healthy children, matched for age, sex, and area, were selected as the control group (CG). RESULTS A total of 2051 questionnaires were collected, with 2039 valid responses. Among them, 151 children had FC, resulting in a prevalence rate of 7.4%. The prevalence rates in boys and girls were 6.6% and 8.5%, respectively, with no significant gender difference (P > 0.05). Alpha diversity analysis revealed higher richness and diversity of intestinal flora in the FCG compared to the CG. At the phylum level, Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes were dominant in both groups. The FCG showed a higher relative abundance of Firmicutes, Actinobacteria, and Proteobacteria compared to the CG (P < 0.05). CONCLUSIONS The prevalence of FC in children aged 0-4 years in Zunyi is 7.4%. Disease characteristics vary with age and living environment but are unrelated to gender. The gut microbiota of children with FC shows significant alterations, with higher diversity and specific phyla abundance.
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Affiliation(s)
- Shungang Gong
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Zhengbo Yu
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Yuan Ding
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Yue Wang
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Xi Li
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Shengli Gu
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China.
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Zhang Y, Zhu M, Dai Y, Gao L, Cheng L. Research Progress in Ulcerative Colitis: The Role of Traditional Chinese Medicine on Gut Microbiota and Signaling Pathways. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2024; 52:2277-2336. [PMID: 39756829 DOI: 10.1142/s0192415x24500885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
Abstract
Ulcerative colitis (UC), one among other refractory diseases worldwide, has shown an increasing trend of progression to colorectal cancer in recent years. In the treatment of UC, traditional Chinese medicine has demonstrated good efficacy, with a high cure rate, fewer adverse effects, great improvement in the quality of patient survival, and reduction in the tendency of cancerous transformation. It shows promise as a complementary and alternative therapy. This review aims to evaluate and discuss the current research on UC, signaling pathways, and gut microbiota. We also summarized the mechanisms of action of various Chinese medicines (active ingredients or extracts) and herbal formulas, through signaling pathways and gut microbiota, with the expectation that they can provide references and evidence for treating UC and preventing inflammation-associated colorectal cancer by traditional Chinese medicine. We illustrate that multiple signaling pathways, such as TLR4, STAT3, PI3K/Akt, NF-[Formula: see text]B, and Keap1/Nrf2, can be inhibited by Chinese herbal treatments through the combined regulation of signaling pathways and gut microbiota, which can act individually or synergistically to inhibit intestinal inflammatory cell infiltration, attenuate gut oxidative responses, and repair the intestinal barrier.
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Affiliation(s)
- Yuyi Zhang
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
| | - Mingfang Zhu
- Graduate School, Zunyi Medical University Zunyi, P. R. China
| | - Yueying Dai
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
| | - Longying Gao
- Department of Anorectal, The First Affiliated Hospital of Heilongjiang, University of Chinese Medicine Harbin, P. R. China
| | - Limin Cheng
- Department of Anorectal, The First Affiliated Hospital of Heilongjiang, University of Chinese Medicine Harbin, P. R. China
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Zhong Y, Chang X, Zhao Z, Zheng L, Kuang G, Li P, Liu C, Fan Y, Liang Z, Zhuang K, Xie Q, Liu Y. Bacteroides fragilis capsular polysaccharide A ameliorates ulcerative colitis in rat by recovering intestinal barrier integrity and restoring gut microbiota. Front Pharmacol 2024; 15:1402465. [PMID: 39776580 PMCID: PMC11703662 DOI: 10.3389/fphar.2024.1402465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 10/02/2024] [Indexed: 01/11/2025] Open
Abstract
Bacteroides fragilis (B. fragilis) is a Gram-negative, obligate anaerobic, commensal bacterium residing in the human gut and holds therapeutic potential for ulcerative colitis (UC). Previous studies have indicated that capsular polysaccharide A (PSA) of B. fragilis is a crucial component for its effectiveness, possessing various biological activities such as anti-inflammatory, anti-tumor, and immune-modulating effects. We previously isolated and characterized the B. fragilis strain ZY-312 from the feces of a healthy breastfed infant, and extracted its PSA, named TP2. In this study, we explored the impact of TP2 on colonic inflammation and delved into its potential mechanisms. Initially, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis in rats and found that TP2 treatment significantly ameliorated TNBS-induced weight loss, increased clinical scores, extensive ulcers, and intestinal epithelial damage in UC rats. Further analysis revealed that TP2 effectively restored the intestinal barrier integrity in UC rats by regulating the expression of Muc-2, tight junction proteins (ZO-1, occludin, claudin-1, and claudin-2), as well as apoptosis-related proteins Bcl-2, BAX, and Cleaved-Caspase-3. Additionally, TP2 suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL23, while promoting the secretion of anti-inflammatory cytokines IL-10 and IL-22, thereby inhibiting the occurrence of inflammation. TP2 also downregulated the phosphorylation levels of AKT and PI3K, effectively inhibiting the abnormal activation of the PI3K/AKT signaling pathway. More interestingly, 16S rRNA sequencing results showed that TP2 restored the ecological imbalance of the rat intestinal microbiota, with an increase in beneficial bacteria such as Lactobacillus and Limosilactobacillus observed in the treatment group. In conclusion, TP2 through the regulation of intestinal barrier-related cells and proteins, inhibition of apoptosis, modulation of inflammation-related cytokine levels, and control of abnormal activation of the PI3K/AKT signaling pathway, restores intestinal barrier integrity. Additionally, by reshaping the ecological imbalance of the gut microbiota, TP2 ultimately alleviates ulcerative colitis in rats.
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Affiliation(s)
- Yijia Zhong
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Xiujuan Chang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Zihan Zhao
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Lijun Zheng
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Gaobo Kuang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Ping Li
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | | | - Yuqin Fan
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Zhixuan Liang
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Ke Zhuang
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Qiuling Xie
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Yangyang Liu
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
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Jin Z, Liu Z, Pan J, Wang S, Cui M, He C, Lin M, Liu X, Yu X, Gong F. FGF20 modulates gut microbiota to mitigate dextran sodium sulfate-induced ulcerative colitis in mouse models. Int Immunopharmacol 2024; 142:113044. [PMID: 39217880 DOI: 10.1016/j.intimp.2024.113044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/24/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC.
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Affiliation(s)
- Zhongqian Jin
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhaoyang Liu
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Jiaxuan Pan
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Shangwen Wang
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mengdie Cui
- Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Chenbei He
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mengyi Lin
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xuehui Liu
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiang Yu
- Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Fanghua Gong
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China.
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Li C, Deng L, Pu M, Ye X, Lu Q. Coptisine alleviates colitis through modulating gut microbiota and inhibiting TXNIP/NLRP3 inflammasome. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118680. [PMID: 39117021 DOI: 10.1016/j.jep.2024.118680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 08/10/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ulcerative colitis (UC) is a disease involving the enteric canal which is characterised by chronisch inflammatory reaction. Coptisine (COP), the distinctive component of Coptis chinensis Franch., is famous for its anti-inflammation, antioxidation, anti-bacteria, and anti-cancer. Earlier researches certified that COP is a prospective remedy for colitis, but the mechanism of colitis and the therapeutical target of COP are deficiently elucidated. AIM OF THIS STUDY In this follow-up study, we adopted dextran sulfate sodium (DSS)-elicited UC model to further elucidate the possible mechanism of COP on UC in mice. MATERIALS AND METHODS COP and the positive drug sulfasalazine (SASP) were administered by oral gavage in DSS-induced colitis mouse model. Oxidative stress, inflammatory cytokines, intestinal barrier permeability, protein expression of the TXNIP/NLRP3 inflammasome pathway and intestinal microbiome structure were assessed. RESULTS Among this investigation, our team discovered that COP could mitigate DSS-elicited UC in murines, with prominent amelioration in weight loss, disease activity index, intestinal permeability (serum diamine oxidase and D-lactate), contracted colonal length and histologic alterations. Furthermore, COP greatly lowered the generation of pro-inflammatory factors, malondialdehyde (MDA) activity and reactive oxygen species (ROS) level, while increased superoxide dismutase (SOD) activity in colonal tissues. Additionally, COP downmodulated the proteic expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, IL-1β and IL-18. Enteric microbiome sequencing displayed that DSS and COP tremendously influenced the constitution and diversity of enteric microbes in DSS-elicited UC murines. Besides, COP elevated the abundance of probiotic bacteria Bacteroidota, Akkermansia_muciniphila and Bacteroides_acidifaciens, lowered the proportions of potential pathogenic bacteria, such as Lachnospiraceae, Acetatifactor_muris, Clostridium_XlVa, Alistipes and Oscillibacter, and reduced the ratio of Bacillota/Bacteroidota, which vastly helped to reverse the enteric microbiome to a balanceable condition. Alterations in these bacteria were strongly correlated with the colitis relative index. CONCLUSION The mechanism of COP against UC is connected with the suppression of TXNIP/NLRP3 inflammasome signalling pathway and the adjustment of the enteric microbiome profiles. The proofs offer new understandings upon the anti-UC function of COP, which might be a prospective candidate against UC.
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Affiliation(s)
- Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, PR China; Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, PR China
| | - Li Deng
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Min Pu
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Xuanlin Ye
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
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Hu Y, Zhou L, Yang J, Bai R, Marchioni E, Zhao M, Zhou L. Anti-inflammatory mechanism of Houttuynia cordata polysaccharides against ulcerative colitis based on multi-omics conjoint analysis. Int J Biol Macromol 2024; 283:137311. [PMID: 39521219 DOI: 10.1016/j.ijbiomac.2024.137311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
The Houttuynia cordata polysaccharide (HCP) was extracted from the traditional Chinese medicine, Houttuynia cordata, known for its anti-inflammatory properties. It has an acidic heteropolysaccharide with a molecular weight of approximately 13.38 kDa, consisting of 7 monosaccharides such as galactose, galacturonic acid, and glucose. Mouse ulcerative colitis (UC) model experiments demonstrated its effective anti-inflammatory activity at concentrations of 100 mg/kg and 300 mg/kg respectively. The objective of this study was to investigate the mechanism of action underlying the therapeutic effects of HCP in UC through omics analysis method. A total of 724 different metabolites and 246 differential lipids were identified. Through metabolomic analysis, six metabolic pathways including the linoleic acid metabolic pathway, caffeine metabolic pathway, mannose and fructose metabolic pathways, methyl histidine metabolic pathway and fatty acid biosynthesis, which were significantly associated with colon-related diseases. Subsequently, lipidomics analysis revealed that the metabolic pathways of α-linolenic and linoleic acid, fatty acid biosynthesis, and glycerolipid metabolism exhibited significant associations with serum lipid metabolism. These findings suggested that HCP had potential therapeutic effects in treating UC.
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Affiliation(s)
- Yueqi Hu
- National Demonstration Center for Experimental Ethnopharmacology Education, School of Pharmaceutical Sciences, South-Central MinZu University, Wuhan 430074, PR China
| | - Li Zhou
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China
| | - Jian Yang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China
| | - Ruibin Bai
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China
| | - Eric Marchioni
- Equipe de Chimie Analytique des Molécules Bioactives et Pharmacognoise, Institut Pluridisciplinaire Hubert Curien (UMR 7178, CNRS/UDS), 74 route du Rhin, 67400 Illkirch, France
| | - Minjie Zhao
- Equipe de Chimie Analytique des Molécules Bioactives et Pharmacognoise, Institut Pluridisciplinaire Hubert Curien (UMR 7178, CNRS/UDS), 74 route du Rhin, 67400 Illkirch, France
| | - Li Zhou
- National Demonstration Center for Experimental Ethnopharmacology Education, School of Pharmaceutical Sciences, South-Central MinZu University, Wuhan 430074, PR China.
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Xiao Q, Luo L, Zhu X, Yan Y, Li S, Chen L, Wang X, Zhang J, Liu D, Liu R, Zhong Y. Formononetin alleviates ulcerative colitis via reshaping the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156153. [PMID: 39423480 DOI: 10.1016/j.phymed.2024.156153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 09/18/2024] [Accepted: 10/11/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND Ulcerative colitis (UC), a type of inflammatory bowel disease, presents substantial challenges in clinical treatment due to the limitations of current medications. Formononetin (FN), a naturally compound with widespread availability, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. PURPOSE This study aimed to investigate the efficacy of FN against UC and its potential regulatory mechanism. METHODS Here, dextran sulfate sodium (DSS) was employed to replicate experimental colitis in mice with concomitant FN treatment. The distribution and localisation of CD68 and F4/80 macrophages in colonic tissues were visualized by immunofluorescence, their chemokine and inflammatory cytokine concentrations were determined by ELISA, and macrophages and M1/M2 subpopulations were determined by flow cytometry. Additionally, 16 s rRNA and LC-MS techniques were used to detect the colonic intestinal microbiota and metabolite profiles, respectively. Correlation analyses was performed to clarify the interactions between differential bacteria, metabolites and M1/M2 macrophages, and pseudo sterile mice were constructed by depletion of gut flora with quadruple antibiotics, followed by faecal microbial transplantation to evaluate its effects on colitis and M1/M2 macrophage polarisation. RESULTS FN dose-dependently alleviated clinical symptoms and inflammatory injury in colonic tissues of colitis mice, with its high-dose efficacy comparable to that of 5-ASA. Concurrently, FN not only inhibited inflammatory infiltration of macrophages and their M1/M2 polarisation balance in colitis mice, but also improved the composition of colonic microbiota and metabolite profiles. However, FN lost its protective effects against DSS-induced colitis and failed to restore the equilibrium of M1/M2 macrophage differentiation following intestinal flora depletion through quadruple antibiotic treatment. Importantly, fecal microbiota transplantation from FN-treated mice restored FN's protective effects against DSS-induced colitis and reestablished its regulatory role in M1/M2 macrophage polarization. CONCLUSION Collectively, FN ameliorated UC through modulating the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.
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Affiliation(s)
- Qiuping Xiao
- College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Effective Material Basis of TCM, Jiangxi Province, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Lin Luo
- College of Acupuncture and Tuina, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Xiyan Zhu
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Yuhao Yan
- College of Acupuncture and Tuina, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Shanshan Li
- Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Liling Chen
- Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Xiaomin Wang
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Jie Zhang
- Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Duanyong Liu
- Jiangxi Provincial Engineering Research Center of Development and Evaluation of TCM classic prescriptions, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Prevention and Treatment of Immunological and Metabolic Diseases Related to Prescription and Syndrome, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Ronghua Liu
- College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Effective Material Basis of TCM, Jiangxi Province, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Youbao Zhong
- College of Acupuncture and Tuina, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Prevention and Treatment of Immunological and Metabolic Diseases Related to Prescription and Syndrome, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
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Singhal S, Bhadana R, Jain BP, Gautam A, Pandey S, Rani V. Role of gut microbiota in tumorigenesis and antitumoral therapies: an updated review. Biotechnol Genet Eng Rev 2024; 40:3716-3742. [PMID: 36632709 DOI: 10.1080/02648725.2023.2166268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Indexed: 01/13/2023]
Abstract
Gut microbiota plays a prominent role in regulation of host nutrientmetabolism, drug and xenobiotics metabolism, immunomodulation and defense against pathogens. It synthesizes numerous metabolites thatmaintain the homeostasis of host. Any disbalance in the normalmicrobiota of gut can lead to pathological conditions includinginflammation and tumorigenesis. In the past few decades, theimportance of gut microbiota and its implication in various diseases, including cancer has been a prime focus in the field of research. Itplays a dual role in tumorigenesis, where it can accelerate as wellas inhibit the process. Various evidences validate the effects of gutmicrobiota in development and progression of malignancies, wheremanipulation of gut microbiota by probiotics, prebiotics, dietarymodifications and faecal microbiota transfer play a significant role.In this review, we focus on the current understanding of theinterrelationship between gut microbiota, immune system and cancer,the mechanisms by which they play dual role in promotion andinhibition of tumorigenesis. We have also discussed the role ofcertain bacteria with probiotic characteristics which can be used tomodulate the outcome of the various anti-cancer therapies under theinfluence of the alteration in the composition of gut microbiota.Future research primarily focusing on the microbiota as a communitywhich affect and modulate the treatment for cancer would benoteworthy in the field of oncology. This necessitates acomprehensive knowledge of the roles of individual as well asconsortium of microbiota in relation to physiology and response ofthe host.
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Affiliation(s)
- Shivani Singhal
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Renu Bhadana
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Buddhi Prakash Jain
- Department of Zoology, Mahatma Gandhi Central University, Motihari, Bihar, India
| | - Akash Gautam
- Centre for Neural and Cognitive Sciences, School of Medical Sciences, University of Hyderabad, Hyderabad, India
| | - Shweta Pandey
- Department of Biotechnology, Govt Vishwanath Yadav Tamaskar Post-Graduate Autonomous College Durg, Chhattisgarh, India
| | - Vibha Rani
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
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Huang J, Zhong Y, Cheng N, Zhang Z, Huang L, Song L, Cheng S, Zhao H, Liu D. Sishen pills inhibit inflammatory dendritic cell differentiation via miR-505-3p mediated E-cadherin downregulation in ulcerative colitis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156035. [PMID: 39342779 DOI: 10.1016/j.phymed.2024.156035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/28/2024] [Accepted: 09/07/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is an autoimmune disease that is highly susceptible to recurrence, which is still a lack of effective drugs with minor side effects in clinic. Intervention of inflammatory differentiation of dendritic cells (DCs) might be an effective strategy to treat UC. Sishen Pills (SSP) is a classic Chinese herbal formula which has been demonstrated the protective effect of UC, but the mechanism remains unclear. PURPOSE To elucidate the protective effects of SSP against UC in mice and reveal its regulatory mechanism of DCs and the key active ingredients for the UC treatment based on transcriptomics, network pharmacology and experiments validation in vivo and vitro. METHOD The key active ingredients of SSP were detected and screened integrating LC-MS/MS and network pharmacology. A mouse UC model was induced with 3% sodium dextran sulfate and treated with SSP for 14 days to evaluate the efficacy. ELISA was used to detect the levels of IL-6, IL-1β and TNF-α in the colon; flow cytometry was used to detect the expression levels of DCs and their subpopulations; whole transcriptomic sequencing of differential RNAs in the colon and RT-PCR to detect key miRNAs to verify the sequencing results. Mouse bone marrow-derived dendritic cells (BMDCs) were isolated, an inflammatory model was constructed using 100 ng/ml LPS, and the effects of SSP on DC proliferation and apoptosis and their surface co-stimulatory molecule expression were examined; IL-6, IL-1β, TNF-α levels were measured by ELISA; RT-PCR and WB were performed to detect miR-505-3p, CDH1, E-cadherin expression. BMDCs with low expression of miR-505-3p were constructed by lentiviral transfection for further validation. The potential key ingredient was re-validated in vivo and vitro experiment. RESULTS Animal experiments showed that SSP alleviated DSS-induced UC symptoms and colonic pathological injury in mice, and inhibited IL-6, IL-1β, TNF-α secretion and inflammatory DC proliferation and activation maturation. Network pharmacology predicted that evodiamine, isobavachalcone, curcumin, and engenol may play a key role in SSP. RNA sequencing revealed that miR-505-3p, as the differential miRNA, shared a large number of transcription factors with E-cadherin, and was involved in inflammatory differentiation regulation. In vivo experiments confirmed that SSP accelerated apoptosis, slowed down proliferation, inhibited inflammatory differentiation and IL-6, IL-1β, and TNF-α secretion in BMDCs, and decreased miR-505-3p, CDH1, and E-cadherin levels. After knocking down miR-505-3p, SSP could not regulate the inflammatory differentiation and IL-6, IL-1β, TNF-α level in BMDCs. Additionally, evodiamine was found and verified to be the key active ingredient of SSP in preventing the inflammatory differatiation of DCs. CONCLUSION SSP prevented the inflammatory differentiation of DCs by downregulating the expression of miR-505-3p, in which Evodiamine may played a key role.
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Affiliation(s)
- Jiaqi Huang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Youbao Zhong
- Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Nian Cheng
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Zheyan Zhang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Li Huang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Lizhao Song
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Shaomin Cheng
- Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
| | - Haimei Zhao
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
| | - Duanyong Liu
- Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; School of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
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