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Olivares C, Ruppé E, Ferreira S, Corbel T, Andremont A, de Gunzburg J, Guedj J, Burdet C. A modelling framework to characterize the impact of antibiotics on the gut microbiota diversity. Gut Microbes 2025; 17:2442523. [PMID: 39711113 DOI: 10.1080/19490976.2024.2442523] [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: 09/13/2024] [Revised: 11/08/2024] [Accepted: 12/09/2024] [Indexed: 12/24/2024] Open
Abstract
Metagenomic sequencing deepened our knowledge about the role of the intestinal microbiota in human health, and several studies with various methodologies explored its dynamics during antibiotic treatments. We compared the impact of four widely used antibiotics on the gut bacterial diversity. We used plasma and fecal samples collected during and after treatment from healthy volunteers assigned to a 5-day treatment either by ceftriaxone (1 g every 24 h through IV route), ceftazidime/avibactam (2 g/500 mg every 8 h through IV route), piperacillin/tazobactam (1 g/500 mg every 8 h through IV route) or moxifloxacin (400 mg every 24 h through oral route). Antibiotic concentrations were measured in plasma and feces, and bacterial diversity was assessed by the Shannon index from 16S rRNA gene profiling. The relationship between the evolutions of antibiotic fecal exposure and bacterial diversity was modeled using non-linear mixed effects models. We compared the impact of antibiotics on gut microbiota diversity by simulation, using various reconstructed pharmacodynamic indices. Piperacillin/tazobactam was characterized by the highest impact in terms of intensity of perturbation (maximal [IQR] loss of diversity of 27.3% [1.9; 40.0]), while moxifloxacin had the longest duration of perturbation, with a time to return to 95% of baseline value after the last administration of 13.2 d [8.3; 19.1]. Overall, moxifloxacin exhibited the highest global impact, followed by piperacillin/tazobactam, ceftazidime/avibactam and ceftriaxone. Their AUC between day 0 and day 42 of the change of diversity indices from day 0 were, respectively, -13.2 Shannon unit.day [-20.4; -7.9], -10.9 Shannon unit.day [-20.4; -0.6] and -10.1 Shannon unit.day [-18.3; -4.6]. We conclude that antibiotics alter the intestinal diversity to varying degrees, both within and between antibiotics families. Such studies are needed to help antibiotic stewardship in using the antibiotics with the lowest impact on the intestinal microbiota.
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Affiliation(s)
| | - Etienne Ruppé
- Université Paris Cité, IAME, INSERM, Paris, France
- APHP, Laboratoire de Bactériologie, Hôpital Bichat, Paris, France
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Palrasu M, Kakar K, Marudamuthu A, Hamida H, Thada S, Zhong Y, Staley S, Busbee PB, Li J, Garcia-Buitrago M, Nagarkatti M, Nagarkatti P. AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis. Gut Microbes 2025; 17:2460538. [PMID: 39894796 PMCID: PMC11792800 DOI: 10.1080/19490976.2025.2460538] [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: 11/02/2024] [Revised: 01/07/2025] [Accepted: 01/26/2025] [Indexed: 02/04/2025] Open
Abstract
Alpha-defensin 1 is a small antimicrobial peptide that acts as the first line of defense against pathogens. It is induced following microbial cues and inflammatory signals in neutrophils and Paneth cells in the small intestine, which suggests that it plays a role in microbial homeostasis in the gut. The gut microbial products also serve as ligands for the aryl hydrocarbon receptor (AhR), an environmental sensor. In the current study, we investigated if there is any crosstalk between AhR and alpha-defensin 1. Interestingly, we found a positive correlation between AhR and alpha-defensin 1 protein levels in ileal tissues from active Crohn's' (CD) patients and epithelial cells (IECs) from multiple models of murine colitis. In vitro downregulation of AhR led to inhibition of α-defensin 1, while activation of AhR induced α-defensin 1 in IECs. AhR directly targeted the dioxin response element 3 (DRE3) region on the α-defensin 1 promoter in IECs. AhR-mediated induction of α-defensin 1 in colitis mice reversed the gut microbial dysbiosis and alleviated colitis. Our data identify a novel signaling pathway in which AhR acts as a transcription factor for α-defensin 1, leading to regulation of homeostasis between gut microbiota, intestinal mucosa, and mucosal immunity.
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Affiliation(s)
- Manikandan Palrasu
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Khadija Kakar
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Amarnath Marudamuthu
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Hamida Hamida
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Shruthi Thada
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Yin Zhong
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Shanieka Staley
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Philip Brandon Busbee
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Jie Li
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA
| | - Monica Garcia-Buitrago
- Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Mitzi Nagarkatti
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Prakash Nagarkatti
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA
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Su F, Su M, Wei W, Wu J, Chen L, Sun X, Liu M, Sun S, Mao R, Bourgonje AR, Hu S. Integrating multi-omics data to reveal the host-microbiota interactome in inflammatory bowel disease. Gut Microbes 2025; 17:2476570. [PMID: 40063366 PMCID: PMC11901428 DOI: 10.1080/19490976.2025.2476570] [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: 12/17/2024] [Revised: 02/14/2025] [Accepted: 03/03/2025] [Indexed: 03/14/2025] Open
Abstract
Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the interactome concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.
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Affiliation(s)
- Fengyuan Su
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Meng Su
- The First Clinical Medical School, Nanfang Hospital of Southern Medical University, Guangzhou, China
| | - Wenting Wei
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Jiayun Wu
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Leyan Chen
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Xiqiao Sun
- Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
| | - Moyan Liu
- Amsterdam UMC location Academic Medical Center, Department of Experimental Vascular Medicine, Amsterdam, The Netherlands
| | - Shiqiang Sun
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Arno R. Bourgonje
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shixian Hu
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Li XL, Megdadi M, Quadri HS. Interaction between gut virome and microbiota on inflammatory bowel disease. World J Methodol 2025; 15:100332. [DOI: 10.5662/wjm.v15.i3.100332] [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: 08/13/2024] [Revised: 12/31/2024] [Accepted: 01/15/2025] [Indexed: 03/06/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic condition marked by recurring gastrointestinal inflammation. While immune, genetic, and environmental factors are well-studied, the gut virome has received less attention. This editorial highlights the work which investigates the gut virome’s role in IBD and its interactions with the bacterial microbiome and host immune system. The gut virome consists of bacteriophages, eukaryotic viruses, and endogenous retroviruses. Among these, Caudovirales bacteriophages are predominant and influence bacterial communities via lysogenic and lytic cycles. Eukaryotic viruses infect host cells directly, while endogenous retroviruses impact gene regulation and immune responses. In IBD, the virome shows distinct alterations, including an increased abundance of Caudovirales phages and reduced Microviridae diversity, suggesting a pro-inflammatory viral environment. Dysbiosis, chronic inflammation, and aberrant immune responses contribute to these changes by disrupting microbial communities and modifying virome composition. Phages affect bacterial dynamics through lysis, lysogeny, and horizontal gene transfer, shaping microbial adaptability and resilience. Understanding these interactions is crucial for identifying novel therapeutic targets and restoring microbial balance in IBD.
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Affiliation(s)
- Xiao-Long Li
- Department of Surgery, Ascension St Agnes Hospital, Baltimore, MD 21009, United States
| | - Mueen Megdadi
- Department of Surgery, Ascension St Agnes Hospital, Baltimore, MD 21009, United States
| | - Humair S Quadri
- Department of Surgery, Ascension St Agnes Hospital, Baltimore, MD 21009, United States
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Hetta HF, Ahmed R, Ramadan YN, Fathy H, Khorshid M, Mabrouk MM, Hashem M. Gut virome: New key players in the pathogenesis of inflammatory bowel disease. World J Methodol 2025; 15:92592. [DOI: 10.5662/wjm.v15.i2.92592] [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: 01/30/2024] [Revised: 05/28/2024] [Accepted: 07/23/2024] [Indexed: 11/27/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the intestine. While the mechanism underlying the pathogenesis of IBD is not fully understood, it is believed that a complex combination of host immunological response, environmental exposure, particularly the gut microbiota, and genetic susceptibility represents the major determinants. The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans. The gut virome varies greatly among individuals and is influenced by factors including lifestyle, diet, health and disease conditions, geography, and urbanization. The majority of research has focused on the significance of gut bacteria in the progression of IBD, although viral populations represent an important component of the microbiome. We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.
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Affiliation(s)
- Helal F Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
- Division of Microbiology, Immunology and Biotechnology, Faculty of pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Rehab Ahmed
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Yasmin N Ramadan
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Hayam Fathy
- Department of Internal Medicine, Division Hepatogastroenterology, Assiut University, Assiut 71515, Egypt
| | - Mohammed Khorshid
- Department of Clinical Research, Egyptian Developers of Gastroenterology and Endoscopy Foundation, Cairo 11936, Egypt
| | - Mohamed M Mabrouk
- Department of Internal Medicine, Faculty of Medicine. Tanta University, Tanta 31527, Egypt
| | - Mai Hashem
- Department of Tropical Medicine, Gastroenterology and Hepatology, Assiut University Hospital, Assiut 71515, Egypt
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Sartor RB. Beyond Random Fecal Microbial Transplants: Next Generation Personalized Approaches to Normalize Dysbiotic Microbiota for Treating IBD. Gastroenterol Clin North Am 2025; 54:333-350. [PMID: 40348491 DOI: 10.1016/j.gtc.2024.11.002] [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] [Indexed: 05/14/2025]
Abstract
This review and commentary outline the strong rationale for normalizing the abnormal microbiota of patients with ulcerative colitis, Crohn's disease, and pouchitis and focus on strategies to improve current variable outcomes of fecal microbial transplant (FMT) in ulcerative colitis. Applying lessons from successful FMT therapy of recurrent Clostridioides difficile and insights from basic scientific understanding of host/microbial interactions provide strategies to enhance clinical outcomes in IBD. We outline promising approaches to develop novel-defined consortia of live biotherapeutic products and combination treatments to improve current results and to optimize and personalize treatment approaches in individual patients and disease subsets.
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Affiliation(s)
- R Balfour Sartor
- Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina - Chapel Hill, Chapel Hill, NC 27517, USA; Department of Microbiology & Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina - Chapel Hill, Chapel Hill, NC 27517, USA.
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7
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Ma Y, Jing J, Gao Y, Yu Y, Mao J, Zhang Y, Li T. MLIF inhibits inflammation and maintains intestinal flora homeostasis in a dextran sulfate sodium (DSS)-induced colitis mouse model. Food Chem Toxicol 2025; 202:115545. [PMID: 40354872 DOI: 10.1016/j.fct.2025.115545] [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: 01/21/2025] [Revised: 04/14/2025] [Accepted: 05/09/2025] [Indexed: 05/14/2025]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disease primarily affecting the colon, characterized by mucosal inflammation and ulceration. Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide derived from Entamoeba histolytica, has demonstrated the anti-inflammatory capacity. The aim of the current work was to test the protective effects of MLIF in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings indicated that MLIF significantly inhibition of colitis development, including body weight, DAI score, colon length, and spleen index. MLIF slowing the progression of inflammation in the colon of mice exposed to DSS, evidenced by HE staining and mRNA expression levels of Il1b, Il6, Il18 and Il10. MLIF significantly alleviated intestinal barrier dysfunction in mice exposed to DSS, evidenced by AB-PAS staining and mRNA expression levels of Tjp1, Ocln and Muc2. Importantly, the administration of MLIF in colitis mice exerted beneficial effects on the gut microbiota, enhancing microbial diversity and abundance, and promoting the restoration of gut microbiota homeostasis. Non-targeted metabolomics results suggest that the benefits of MLIF may arise from its modulation of tryptophan metabolism pathways. In conclusion, MLIF prevention inflammation induction and preserves intestinal homeostasis against colitis induced by DSS.
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Affiliation(s)
- Yulin Ma
- Department of Pharmacy, Punan Hospital, Pudong New District, Shanghai, 200125, China; School of Medicine, Shanghai University, Shanghai, 200444, China
| | - Jing Jing
- Department of Pharmacy, Punan Hospital, Pudong New District, Shanghai, 200125, China
| | - Yuan Gao
- School of Medicine, Shanghai University, Shanghai, 200444, China
| | - Yongsheng Yu
- School of Medicine, Shanghai University, Shanghai, 200444, China
| | - Junqin Mao
- Department of Clinical Pharmacy, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201803, China
| | - Yuefan Zhang
- School of Medicine, Shanghai University, Shanghai, 200444, China
| | - Tiejun Li
- Department of Pharmacy, Punan Hospital, Pudong New District, Shanghai, 200125, China.
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Yang B, Tan M, Xiong F. Global trends in osteoimmunology and osteoporosis research: A bibliometric analysis from 2013 to 2022. Medicine (Baltimore) 2025; 104:e42367. [PMID: 40324222 PMCID: PMC12055078 DOI: 10.1097/md.0000000000042367] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 03/28/2025] [Accepted: 04/17/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND A large number of studies have shown that osteoporosis is closely related to bone immunology. The purpose of this study is to conduct bibliometrics and visual analysis of the fields related to osteoimmunology and osteoporosis from 2013 to 2022 and to summarize the research hotspots and trends in this field. METHODS We searched the Web of Science core collection database for articles on osteoimmunology and osteoporosis published between 2013 and 2022. Vosviewer 1.6.18 and CiteSpace.6.2. R4 were used to analyze the retrieved data. RESULTS A total of 3218 articles on osteoimmunology and osteoporosis were included in this study. A total of 76 countries, 347 institutions, and 502 authors were included in the articles examined in this study. The main research countries were China, the United States, and South Korea. Shanghai Jiaotong University, Harvard University, and the University of California system were the main research institutions. The author who published the most papers was Xu, Jiake. CONCLUSIONS This study is the first to summarize the global research trends in the field of osteoimmunology and osteoporosis from 2013 to 2022. That helps researchers quickly understand the research hotspots and directions in this field.
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Affiliation(s)
- Bencheng Yang
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Mingshuai Tan
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Fusheng Xiong
- Department of Spine Surgery, Suining Municipal Hospital of Traditional Chinese Medicine, Suining, Sichuan, China
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Guo B, Zhang W, Zou J, Sun L, Dong N, Liu B. β-1,3-glucans from Euglena Gracilis protects against ulcerative colitis via modulating the gut barrier, T-cell immunity and gut microbiota. Int J Biol Macromol 2025; 305:141288. [PMID: 39984099 DOI: 10.1016/j.ijbiomac.2025.141288] [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: 12/16/2024] [Revised: 02/11/2025] [Accepted: 02/17/2025] [Indexed: 02/23/2025]
Abstract
Ulcerative colitis (UC) is characterized by impaired gut barrier, dysregulated immune responses and pronounced gut dysbiosis. Euglena gracilis (EG), rich in β-1,3-glucan (EGP), exhibits immunomodulatory properties, yet its effects on colitis and EGP's role as a core bioactive component are unclear. The aim of this study was to investigate the protective effects of EGP against UC by targeting gut barrier, T-cell immunity and gut microbiota. Results indicated that EG and EGP effectively improved the body weight, colon growth and reduced disease activity index of the DSS-induced mice. Both treatments also significantly suppressed the level of TNF-α and IL-6, restored gut barrier by upregulating ZO-1 and balanced Th17/Treg cells ratio. Microbiota analysis revealed EG and EGP reshaped gut microbiota composition, with an increase in beneficial strains, particularly within the Bacteroidota phylum. Metabolomics linked these changes to enhanced amino acid metabolism. Bacteroides fragilis, a Bacteroidota member, displayed similar anti-colitis bioactivity. In vitro fermentation with fecal samples from UC patients confirmed EGP's role in reshaping gut microbiota, increasing beneficial families such as Clostridiaceae and Lactobacillaceae, while enhancing tryptophan metabolism with anti-inflammatory indoles. These findings identify EGP as the core active component of EG, highlighting its potential in UC prevention through microbiota modulation, gut barrier support and immune regulation.
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Affiliation(s)
- Bingbing Guo
- College of Chemistry and Life Science, Beijing University of Technology, Beijing, China
| | - Weihao Zhang
- College of Chemistry and Life Science, Beijing University of Technology, Beijing, China
| | - Jingwen Zou
- College of Chemistry and Life Science, Beijing University of Technology, Beijing, China
| | - Liqin Sun
- School of Life Sciences, Yantai University, Yantai, China
| | - Ningning Dong
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University/National Clinical Research Center of Gastrointestinal Disease/Beijing Digestive Disease Center/Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
| | - Bin Liu
- School of Life Sciences, Yantai University, Yantai, China; Shenzhen Key Laboratory of Food Nutrition and Health, Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen, China.
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10
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Pope Q, Varma R, Tataru C, David MM, Fern X. Learning a deep language model for microbiomes: The power of large scale unlabeled microbiome data. PLoS Comput Biol 2025; 21:e1011353. [PMID: 40334224 PMCID: PMC12058177 DOI: 10.1371/journal.pcbi.1011353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 03/24/2025] [Indexed: 05/09/2025] Open
Abstract
We use open source human gut microbiome data to learn a microbial "language" model by adapting techniques from Natural Language Processing (NLP). Our microbial "language" model is trained in a self-supervised fashion (i.e., without additional external labels) to capture the interactions among different microbial taxa and the common compositional patterns in microbial communities. The learned model produces contextualized taxon representations that allow a single microbial taxon to be represented differently according to the specific microbial environment in which it appears. The model further provides a sample representation by collectively interpreting different microbial taxa in the sample and their interactions as a whole. We demonstrate that, while our sample representation performs comparably to baseline models in in-domain prediction tasks such as predicting Irritable Bowel Disease (IBD) and diet patterns, it significantly outperforms them when generalizing to test data from independent studies, even in the presence of substantial distribution shifts. Through a variety of analyses, we further show that the pre-trained, context-sensitive embedding captures meaningful biological information, including taxonomic relationships, correlations with biological pathways, and relevance to IBD expression, despite the model never being explicitly exposed to such signals.
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Affiliation(s)
- Quintin Pope
- School of Electrical Engineering and Computer Science, Oregon State University, Corvallis, Oregon, United States of America
| | - Rohan Varma
- School of Electrical Engineering and Computer Science, Oregon State University, Corvallis, Oregon, United States of America
| | - Christine Tataru
- Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America
| | - Maude M David
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, United States of America
| | - Xiaoli Fern
- School of Electrical Engineering and Computer Science, Oregon State University, Corvallis, Oregon, United States of America
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11
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Medjbeur T, Sardo U, Perrier P, Cormier K, Roy M, Dumay A, Kautz L. Comparative analysis of dietary iron deprivation and supplementation in a murine model of colitis. FASEB Bioadv 2025; 7:e70007. [PMID: 40330433 PMCID: PMC12050954 DOI: 10.1096/fba.2025-00022] [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: 01/22/2025] [Revised: 02/20/2025] [Accepted: 02/21/2025] [Indexed: 05/08/2025] Open
Abstract
Inflammatory bowel diseases are chronic inflammatory conditions with growing prevalence in western populations. Iron is an essential component of erythrocytes hemoglobin. Under the influence of elevated hepcidin production, iron is sequestered in cells during inflammation which, in turn, leads to iron restriction for red blood cell synthesis. As a consequence, iron deficiency and anemia of inflammation are the most prevalent extraintestinal complications in IBD patients. Iron deficiency is commonly treated with oral iron supplements, with limited efficacy as iron absorption is blunted during intestinal inflammation. Moreover, iron supplementation can cause intestinal complications, as previous studies have shown that it can worsen the inflammatory response. However, a comparative analysis of the effects of low, adequate, and high dietary iron content matching the iron supplementation given to patients has not been performed in mice. We therefore tested the impact of dietary iron deprivation and supplementation in a murine model of colitis induced by dextran sodium sulfate. We found that both dietary iron deprivation and supplementation were accompanied by a more severe inflammation with earlier signs of gastrointestinal bleeding compared to mice fed an iron-adequate diet. The manipulation of dietary iron led to a profound dysbiosis in the colon of control mice that differed depending on the dietary iron content. Analysis of this dysbiosis is in line with a pronounced susceptibility to colonic inflammation, thus questioning the benefit/risk balance of oral iron supplementation for IBD patients.
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Affiliation(s)
- Thanina Medjbeur
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III – Paul Sabatier (UPS)ToulouseFrance
| | - Ugo Sardo
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III – Paul Sabatier (UPS)ToulouseFrance
| | - Prunelle Perrier
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III – Paul Sabatier (UPS)ToulouseFrance
| | - Kevin Cormier
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III – Paul Sabatier (UPS)ToulouseFrance
| | - Maryline Roy
- Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche Sur l'Inflammation, Inflamex Laboratory of ExcellenceParisFrance
| | - Anne Dumay
- Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche Sur l'Inflammation, Inflamex Laboratory of ExcellenceParisFrance
| | - Léon Kautz
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III – Paul Sabatier (UPS)ToulouseFrance
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12
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Chulkina M, Tran H, Uribe G, McAninch SB, McAninch C, Seideneck A, He B, Lanza M, Khanipov K, Golovko G, Powell DW, Davenport ER, Pinchuk IV. MyD88-mediated signaling in intestinal fibroblasts regulates macrophage antimicrobial defense and prevents dysbiosis in the gut. Cell Rep 2025; 44:115553. [PMID: 40257864 DOI: 10.1016/j.celrep.2025.115553] [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: 08/02/2024] [Revised: 02/03/2025] [Accepted: 03/20/2025] [Indexed: 04/23/2025] Open
Abstract
Fibroblasts that reside in the gut mucosa are among the key regulators of innate immune cells, but their role in the regulation of the defense functions of macrophages remains unknown. MyD88 is suggested to shape fibroblast responses in the intestinal microenvironment. We found that mice lacking MyD88 in fibroblasts showed a decrease in the colonic antimicrobial defense, developing dysbiosis and aggravated dextran sulfate sodium (DSS)-induced colitis. These pathological changes were associated with the accumulation of Arginase 1+ macrophages with low antimicrobial defense capability. Mechanistically, the production of interleukin (IL)-6 and CCL2 downstream of MyD88 was critically involved in fibroblast-mediated support of macrophage antimicrobial function, and IL-6/CCL2 neutralization resulted in the generation of macrophages with decreased production of the antimicrobial peptide cathelicidin and impaired bacterial clearance. Collectively, these findings revealed a critical role of fibroblast-intrinsic MyD88 signaling in regulating macrophage antimicrobial defense under colonic homeostasis, and its disruption results in dysbiosis, predisposing the host to the development of intestinal inflammation.
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Affiliation(s)
- Marina Chulkina
- The Pennsylvania State University, College of Medicine, Department of Medicine, Hershey, PA, USA
| | - Hanh Tran
- The Pennsylvania State University, Department of Biology, Huck Institute of the Life Sciences, University Park, PA, USA
| | - Gabriela Uribe
- The Pennsylvania State University, College of Medicine, Department of Medicine, Hershey, PA, USA
| | - Steven Bruce McAninch
- The Pennsylvania State University, College of Medicine, Department of Medicine, Hershey, PA, USA
| | - Christina McAninch
- The Pennsylvania State University, College of Medicine, Department of Medicine, Hershey, PA, USA
| | - Ashley Seideneck
- The Pennsylvania State University, College of Medicine, Department of Medicine, Hershey, PA, USA
| | - Bing He
- The Pennsylvania State University, College of Medicine, Department of Medicine, Hershey, PA, USA
| | - Matthew Lanza
- The Pennsylvania State University, College of Medicine, Department of Comparative Medicine, Hershey, PA, USA
| | - Kamil Khanipov
- The University of Texas Medical Branch, Department of Pharmacology, Galveston, TX, USA
| | - Georgiy Golovko
- The University of Texas Medical Branch, Department of Pharmacology, Galveston, TX, USA
| | - Don W Powell
- The University of Texas Medical Branch, Department of Internal Medicine, Galveston, TX, USA
| | - Emily R Davenport
- The Pennsylvania State University, Department of Biology, Huck Institute of the Life Sciences, University Park, PA, USA
| | - Irina V Pinchuk
- The Pennsylvania State University, College of Medicine, Department of Medicine, Hershey, PA, USA.
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13
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Fehily SR, Wright EK, Basnayake C, Wilson-O'Brien AL, Stanley A, Marks EP, Russell EE, Hamilton AL, Bryant RV, Costello SP, Kamm MA. Faecal microbiota transplantation in Crohn's disease: an Australian randomised placebo-controlled trial protocol. BMJ Open 2025; 15:e094714. [PMID: 40254304 PMCID: PMC12010309 DOI: 10.1136/bmjopen-2024-094714] [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: 10/07/2024] [Accepted: 03/24/2025] [Indexed: 04/22/2025] Open
Abstract
INTRODUCTION The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence. METHODS AND ANALYSIS At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease. ETHICS AND DISSEMINATION Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.
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Affiliation(s)
- Sasha R Fehily
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Chamara Basnayake
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Amy L Wilson-O'Brien
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Annalise Stanley
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Elise P Marks
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Erin E Russell
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Amy L Hamilton
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Robert V Bryant
- Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
| | - Sam P Costello
- Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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14
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Rahaman MM, Wangchuk P, Sarker S. A systematic review on the role of gut microbiome in inflammatory bowel disease: Spotlight on virome and plant metabolites. Microb Pathog 2025; 205:107608. [PMID: 40250496 DOI: 10.1016/j.micpath.2025.107608] [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: 08/02/2024] [Revised: 04/14/2025] [Accepted: 04/16/2025] [Indexed: 04/20/2025]
Abstract
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.
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Affiliation(s)
- Md Mizanur Rahaman
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, 4811, Australia
| | - Phurpa Wangchuk
- College of Science and Engineering, James Cook University, Nguma Bada campus, McGregor Rd, Smithfield, Cairns, QLD 4878, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Nguma Bada campus, McGregor Rd, Smithfield, Cairns, QLD, 4878, Australia
| | - Subir Sarker
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, 4811, Australia.
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15
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He B, Duan T, Hu D, Chen L, Qiao L, Song D, Wang L, Fan S, Teng K, Wang W, Li A. Lactobacillus plantarum 17-1 Ameliorates DSS-Induced Colitis by Modulating the Colonic Microbiota Composition and Metabolome in Mice. Nutrients 2025; 17:1348. [PMID: 40284212 PMCID: PMC12030267 DOI: 10.3390/nu17081348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/05/2025] [Accepted: 04/10/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Lactobacillus strains are widely used as probiotics in the functional food industry and show potential for treating inflammatory bowel disease (IBD). However, the strain specificity and limited stress resistance of Lactobacillus restricts its therapeutic effectiveness. The aim of this study was to investigate the effects of dietary supplementation with microencapsulated Lactobacillus plantarum 17-1 on the intestinal immune responses, gut microbiota composition, and metabolic characteristics in colitis mice. Methods: Mice were pre-fed a diet containing microencapsulated Lactobacillus plantarum 17-1 for 3 weeks and then treated with 2.5% dextran sulfate sodium (DSS) in drinking water for 8 days to induce colitis. Results: The results showed that microencapsulated Lactobacillus plantarum 17-1 effectively alleviated clinical symptoms and histopathological features of colitis mice and suppressed the up-regulation of pro-inflammatory cytokines IL-6 and IL-17 in the colon of colitis mice. Additionally, Lactobacillus plantarum 17-1 significantly increased the relative abundance of several beneficial bacterial taxa, including Ruminococcaceae_UCG_014, Bacteroides, Prevotellaceae_UCG_001, Lactococcus, Weissella, Pediococcus, and so on. Moreover, it regulated the levels of multiple inflammation-related metabolites involved in linolenic acid metabolism, arachidonic acid metabolism, primary bile acid biosynthesis, and tyrosine metabolism. Conclusions: These results suggest that dietary supplementation with microencapsulated Lactobacillus plantarum 17-1 reduced colitis inflammation in mice by modulating the intestinal microbiota composition and metabolic characteristics, which may serve as a potential therapeutic strategy for IBD.
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Affiliation(s)
- Beibei He
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Tao Duan
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Dandan Hu
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
- Faculty of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
| | - Lixian Chen
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Lin Qiao
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Dan Song
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Li Wang
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Shijie Fan
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Kunru Teng
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Weiwei Wang
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
| | - Aike Li
- Academy of National Food and Strategic Reserves Administration, Beijing 100037, China; (B.H.); (T.D.); (D.H.); (L.C.); (L.Q.); (D.S.); (L.W.); (S.F.); (K.T.)
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16
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El Boukhari R, Matin M, Bouissane L, Ławiński M, Lushchak O, Singla RK, Mickael M, Mayneris‐Perxachs J, Grafakou ME, Xu S, Liu B, Guan J, Półtorak A, Szpicer A, Wierzbicka A, Tzvetkov NT, Banach M, Horbańczuk JO, Jóźwik A, Cascella M, Shen B, Pirgozliev VR, Wang D, Litvinova O, Adamska O, Kamińska A, Łapiński M, Stolarczyk A, Berindan‐Neagoe I, Milella L, Yeung AWK, Suravajhala P, Bishayee A, Lordan R, Iantovics LB, Lagoa R, Michalczuk M, Stoyanov J, Kinghorn AD, Jalil B, Weckwerth W, Goh BH, Li M, Chaubey G, Russo GL, Frazzini S, Rossi L, Battino M, Jia W, Su Q, Ma X, Rollinger JM, Rittmann SKR, Sheridan H, Walsh JJ, Lizard G, Karpiński TM, Silva AS, Piwowarski J, Xie L, Fan T, Giampieri F, El Midaoui A, Wong K, Gan R, Fatimi A, Atanasov AG. Enhancing human gut health: Global innovations in dysbiosis management. IMETA 2025. [DOI: 10.1002/imt2.70028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/26/2025] [Indexed: 05/03/2025]
Affiliation(s)
- Reda El Boukhari
- Chemical Science and Engineering Research Team (ERSIC), Department of Chemistry, Polydisciplinary Faculty of Beni Mellal (FPBM) Sultan Moulay Slimane University (USMS) Beni Mellal Morocco
| | - Maima Matin
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrzębiec Poland
| | - Latifa Bouissane
- Molecular Chemistry, Materials and Catalysis Laboratory, Faculty of Sciences and Technologies Sultan Moulay Slimane University Beni Mellal Morocco
| | - Michał Ławiński
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrzębiec Poland
- Department of General, Gastroenterologic and Oncologic Surgery Medical University of Warsaw Warsaw Poland
| | - Oleh Lushchak
- Department of Biochemistry and Biotechnology Vasyl Stefanyk Precarpathian National University Ivano‐Frankivsk Ukraine
- Research and Development University Ivano‐Frankivsk Ukraine
| | - Rajeev K. Singla
- Department of Pharmacy and Institutes for Systems Genetics, Center for High Altitude Medicine, Frontiers Science Center for Disease‐related Molecular Network, West China Hospital Sichuan University Chengdu Sichuan China
- School of Pharmaceutical Sciences Lovely Professional University Phagwara Punjab India
| | - Michel‐Edwar Mickael
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrzębiec Poland
| | - Jordi Mayneris‐Perxachs
- Department of Diabetes, Endocrinology and Nutrition Dr. Josep Trueta University Hospital Girona Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) Madrid Spain
- Integrative Systems Medicine and Biology Group, Girona Biomedical Research Institute (IDIBGI‐CERCA) Parc Hospitalari Martí i Julià Salt Spain
| | - Maria Eleni Grafakou
- Chair of Pharmaceutical Biology, Faculty of Pharmacy and Chemistry University of Regensburg Germany
| | - Shuhua Xu
- Center for Evolutionary Biology, School of Life Sciences Fudan University Shanghai China
- Human Phenome Institute, Zhangjiang Fudan International Innovation Center Fudan University Shanghai China
| | - Bowen Liu
- School of Agriculture Yunnan University Kunming China
| | - Jiayi Guan
- Henan Institute of Medical and Pharmaceutical Sciences Zhengzhou University Zhengzhou China
| | - Andrzej Półtorak
- Department of Technique and Food Development, Institute of Human Nutrition Sciences Warsaw University of Life Sciences Warsaw Poland
| | - Arkadiusz Szpicer
- Department of Technique and Food Development, Institute of Human Nutrition Sciences Warsaw University of Life Sciences Warsaw Poland
| | - Agnieszka Wierzbicka
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrzębiec Poland
- Department of Technique and Food Development, Institute of Human Nutrition Sciences Warsaw University of Life Sciences Warsaw Poland
| | - Nikolay T. Tzvetkov
- Department of Biochemical Pharmacology and Drug Design, Institute of Molecular Biology “Roumen Tsanev” Bulgarian Academy of Sciences Sofia Bulgaria
| | - Maciej Banach
- Faculty of Medicine The John Paul II Catholic University of Lublin (KUL) Lublin Poland
- Department of Cardiology and Adult Congenital Heart Diseases Polish Mother's Memorial Hospital Research Institute (PMMHRI) Lodz Poland
- Department of Preventive Cardiology and Lipidology Medical University of Lodz (MUL) Lodz Poland
- Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins University School of Medicine Baltimore Maryland USA
| | - Jarosław Olav Horbańczuk
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrzębiec Poland
| | - Artur Jóźwik
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrzębiec Poland
| | - Marco Cascella
- Anesthesia and Pain Medicine, Department of Medicine, Surgery and Dentistry “Scuola MedicaSalernitana” University of Salerno Baronissi Italy
| | - Bairong Shen
- Department of Critical Care Medicine and Institutes for Systems Genetics Frontiers Science Center for Disease‐Related Molecular Network, West China Hospital,Sichuan University Chengdu Sichuan China
- Center for High Altitude Medicine, West China Hospital Sichuan University Chengdu Sichuan China
| | | | - Dongdong Wang
- Centre for Metabolism, Obesity and Diabetes Research McMaster University Hamilton Ontario Canada
- Division of Endocrinology and Metabolism, Department of Medicine McMaster University Hamilton Ontario Canada
| | - Olena Litvinova
- National University of Pharmacy of the Ministry of Health of Ukraine Kharkiv Ukraine
- Ludwig Boltzmann Institute Digital Health and Patient Safety Medical University of Vienna Vienna Austria
| | - Olga Adamska
- Faculty of Medicine Collegium Medicum Cardinal Stefan Wyszyński University in Warsaw Warsaw Poland
| | - Agnieszka Kamińska
- Faculty of Medicine Collegium Medicum Cardinal Stefan Wyszyński University in Warsaw Warsaw Poland
| | - Marcin Łapiński
- Orthopaedic and Rehabilitation Department Medical University of Warsaw Warsaw Poland
| | - Artur Stolarczyk
- Orthopaedic and Rehabilitation Department Medical University of Warsaw Warsaw Poland
| | - Ioana Berindan‐Neagoe
- Department of Genomics MEDFUTURE ‐ Institute for Biomedical Research“Iuliu Hațieganu” University of Medicine and Pharmacy No. 23 Cluj‐Napoca Romania
| | - Luigi Milella
- Department of Health Sciences University of Basilicata Potenza Italy
| | - Andy Wai Kan Yeung
- Oral and Maxillofacial Radiology, Applied Oral Sciences and Community Dental Care, Faculty of Dentistry The University of Hong Kong Pokfulam Hong Kong SAR
| | - Prashanth Suravajhala
- Amrita School of Biotechnology Amrita Viswa Vidyapeetham Clappana Kerala India
- Department of Biosciences Manipal University Jaipur, Dehmi Kala Jaipur Rajasthan India
| | - Anupam Bishayee
- Department of Pharmacology College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine Bradenton Florida USA
| | - Ronan Lordan
- The Institute for Translational Medicine and Therapeutics, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA
| | - Laszlo Barna Iantovics
- Department of Electrical Engineering and Information Technology George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures Targu Mures Romania
| | - Ricardo Lagoa
- ESTG‐Polytechnic Institute of Leiria Morro do Lena‐Alto do Vieiro Leiria Portugal
- LSRE‐LCM‐Associate Laboratory in Chemical Engineering University of Porto Porto Portugal
| | - Monika Michalczuk
- Department of Animal Breeding, Institute of Animal Sciences Warsaw University of Life Sciences ‐ SGGW Warsaw Poland
| | - Jivko Stoyanov
- Swiss Paraplegic Research Nottwil Switzerland
- Institute of Social and Preventive Medicine (ISPM) University of Bern Bern Switzerland
| | | | - Banaz Jalil
- Pharmacognosy and Phytotherapy UCL School of Pharmacy London UK
| | - Wolfram Weckwerth
- Molecular Systems Biology Lab (MOSYS), Department of Functional and Evolutionary Ecology University of Vienna Vienna Austria
- Vienna Metabolomics Center (VIME) University of Vienna Vienna Austria
| | - Bey Hing Goh
- Sunway Biofunctional Molecules Discovery Centre (SBMDC) School of Medical and Life Sciences Subang Jaya Malaysia
- Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy Monash University Malaysia Subang Jaya Malaysia
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine University of Technology Sydney Ultimo New South Wales Australia
| | - Meng‐Yao Li
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
- Department of Biliary‐Pancreatic Surgery, Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
| | - Gyaneshwer Chaubey
- Cytogenetics Laboratory, Department of Zoology Banaras Hindu University Varanasi Uttar Pradesh India
| | - Gian Luigi Russo
- National Research Council Institute of Food Sciences Avellino Italy
| | - Sara Frazzini
- Department of Veterinary Medicine and Animal Science (DIVAS) University of Milan Lodi Italy
| | - Luciana Rossi
- Department of Veterinary Medicine and Animal Science (DIVAS) University of Milan Lodi Italy
| | - Maurizio Battino
- Department of Clinical Sciences Polytechnic University of Marche Ancona Italy
- Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods Polytechnic University of Marche (Italy), Universidad Europea del Atlántico (Spain), and Jiangsu University (China) Ancona Italy
- International Joint Research, Laboratory of Intelligent Agriculture and Agri‐Products Processing Jiangsu University Zhenjiang China
| | - Wei Jia
- Department of Pharmacology and Pharmacy The University of Hong Kong Pokfulam Hong Kong SAR
| | - Qi Su
- Microbiota I‐Center Shatin Hong Kong SAR
- Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong SAR
| | - Xiaoqiang Ma
- Department of Food Science and Technology, School of Agriculture and Biology Shanghai Jiao Tong University Shanghai China
| | - Judith M. Rollinger
- Division of Pharmacognosy, Department of Pharmaceutical Sciences, Faculty of Life Sciences University of Vienna Vienna Austria
| | - Simon K.‐M. R. Rittmann
- Archaea Physiology & Biotechnology Group, Department of Functional and Evolutionary Ecology University of Vienna Vienna Austria
| | - Helen Sheridan
- The NatPro Centre & School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin Dublin Ireland
- Université Bourgogne Europe/INSERM, 21000 Dijon and PHYNOHA Consulting Fontaine‐lès‐Dijon France
| | - John J. Walsh
- The NatPro Centre & School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin Dublin Ireland
| | - Gérard Lizard
- Université Bourgogne Europe/INSERM, 21000 Dijon and PHYNOHA Consulting Fontaine‐lès‐Dijon France
| | - Tomasz M. Karpiński
- Department of Medical Microbiology Poznań University of Medical Sciences Poznań Poland
| | - Ana Sanches Silva
- University of Coimbra, Faculty of Pharmacy, Polo III, Azinhaga de Santa Comba Coimbra Portugal
- Centre for Animal Science Studies (CECA), ICETA University of Porto Porto Portugal
| | - Jakub Piwowarski
- Microbiota Lab, Department of Pharmaceutical Microbiology and Bioanalysis Medical University of Warsaw Warsaw Poland
| | - Liwei Xie
- State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology Institute of Microbiology, Guangdong Academy of Sciences Guangzhou China
- School of Life & Health Sciences Fuyao University of Science & Technology Fuzhou Fujian China
| | - Tai‐Ping Fan
- School of Life & Health Sciences Fuyao University of Science & Technology Fuzhou Fujian China
| | - Francesca Giampieri
- Department of Clinical Sciences Polytechnic University of Marche Ancona Italy
- Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods Polytechnic University of Marche (Italy), Universidad Europea del Atlántico (Spain), and Jiangsu University (China) Ancona Italy
- Research Group on Food, Nutritional Biochemistry and Health Universidad Europea del Atlántico Santander Spain
- International Research Center for Food Nutrition and Safety Jiangsu University Zhenjiang China
| | - Adil El Midaoui
- Faculty of Sciences and Techniques Errachidia, Moulay Ismail University of Meknes Meknes Morocco
- Department of Pharmacology and Physiology, Faculty of Medicine University of Montreal Montreal Quebec Canada
| | - Ka‐Hing Wong
- Research Institute for Future Food The Hong Kong Polytechnic University Hung Hom Hong Kong SAR
- Department of Food Science and Nutrition The Hong Kong Polytechnic University Hung Hom Hong Kong SAR
| | - Ren‐You Gan
- Research Institute for Future Food The Hong Kong Polytechnic University Hung Hom Hong Kong SAR
- Department of Food Science and Nutrition The Hong Kong Polytechnic University Hung Hom Hong Kong SAR
| | - Ahmed Fatimi
- Chemical Science and Engineering Research Team (ERSIC), Department of Chemistry, Polydisciplinary Faculty of Beni Mellal (FPBM) Sultan Moulay Slimane University (USMS) Beni Mellal Morocco
| | - Atanas G. Atanasov
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrzębiec Poland
- Ludwig Boltzmann Institute Digital Health and Patient Safety Medical University of Vienna Vienna Austria
- Laboratory of Natural Products and Medicinal Chemistry (LNPMC), Center for Global Health Research, Saveetha Medical College and Hospital Saveetha Institute of Medical and Technical Sciences (SIMATS) Thandalam Chennai India
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17
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Xiao Y, Yue X, Zhang X, Yang Y, Zhang Y, Sun L. The role of bacteriophage in inflammatory bowel disease and its therapeutic potential. Crit Rev Microbiol 2025:1-15. [PMID: 40219702 DOI: 10.1080/1040841x.2025.2492154] [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: 08/02/2024] [Revised: 03/25/2025] [Accepted: 04/07/2025] [Indexed: 04/14/2025]
Abstract
Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders impacting the gastrointestinal (GI) tract. It represents a significant public health challenge due to its rising global incidence and substantial impact on patients' quality of life. Emerging research suggests a pivotal role of the human microbiome in IBD pathogenesis. Bacteriophages, integral components of the human microbiome, are indicated to influence the disease onset, progression, and therapeutic strategies. Here, we review the effect of bacteriophages on the pathogenesis of IBD and, more specifically, on the gut bacteria, the systemic immunity, and the susceptibility genes. Additionally, we explore the potential therapeutic use of the bacteriophages to modify gut microbiota and improve the health outcomes of IBD patients. This review highlights the potential of therapeutic bacteriophages in regulating gut microbiota and modulating the immune response to improve health outcomes in IBD patients. Future studies on personalized bacteriophage therapy and its integration into clinical practice could advance treatment strategies for IBD.
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Affiliation(s)
- Yuyang Xiao
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xinyu Yue
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Xupeng Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yifei Yang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Yibo Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Lang Sun
- Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
- Department of Microbiology, Xiangya School of the Basic Medical Science, Central South University, Changsha, Hunan Province, China
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18
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Zhang Y, Zhao Q, Wu Z, Chen N, Li N, Liu J, Zhang M, Li S, Chi Y, Liu Y. Mesenteric Lymphatic B Cells Migrate to the Gut and Aggravate TNBS-Induced Rat Colitis via Regulating Intestinal T Cells. Int J Mol Sci 2025; 26:3519. [PMID: 40331987 PMCID: PMC12026553 DOI: 10.3390/ijms26083519] [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: 02/06/2025] [Revised: 04/01/2025] [Accepted: 04/07/2025] [Indexed: 05/08/2025] Open
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is affecting a growing global population. Unlike UC, which is characterized by inflammation confined to the intestinal mucosa and submucosa, CD involves transmural inflammation of the intestine. Although the lymphatic system is believed to play a role in the pathogenesis of CD, its exact contribution remains poorly understood. Mesenteric lymphatics (MLs), which drain interstitial fluid and immune cells into mesenteric lymph nodes, have been implicated in this process. In the present study, we aimed to investigate the role of ML immune cells in TNBS-induced colitis in rats. Flow cytometry analysis revealed an increased ratio of B cells and altered B cell function in the MLs of colitis rats compared to controls. The adoptive transfer of mesenteric lymphatic B (MLB) cells isolated from colitis rats to recipient rats exacerbated colitis and was associated with the enhanced migration of MLB cells to the gut. RNA sequencing analysis demonstrated a significant upregulation of genes associated with inflammation and immune responses in MLB cells from colitis rats, particularly key molecules involved in T cell activation, such as cluster of differentiation 27 (Cd27) and cluster of differentiation 40 (Cd40), and the chemotactic receptor C-C motif chemokine receptor 8 (Ccr8), which mediates B cell migration in response to T cells. Mechanistically, MLB cells from colitis rats were recruited to the colon by intra-intestinal T cells through the Ccr8-C-C motif chemokine ligand 1 (Ccl1) axis, where they subsequently exacerbated inflammatory responses via enhanced differentiation. These observations indicate that the migration of MLB cells to the gut exacerbates TNBS-induced colitis in rats by modulating intestinal T cells.
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Affiliation(s)
- Yu Zhang
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China; (Y.Z.); (Q.Z.); (Z.W.); (N.C.)
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
| | - Qinghe Zhao
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China; (Y.Z.); (Q.Z.); (Z.W.); (N.C.)
- Department of Central Laboratory and Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China;
| | - Zhe Wu
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China; (Y.Z.); (Q.Z.); (Z.W.); (N.C.)
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
| | - Ning Chen
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China; (Y.Z.); (Q.Z.); (Z.W.); (N.C.)
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
| | - Na Li
- Department of Central Laboratory and Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China;
| | - Jiao Liu
- Center of Medical and Health Analysis, Peking University Health Science Center, Beijing 100191, China;
| | - Menglei Zhang
- Department of Animal Laboratory, Peking University People’s Hospital, Beijing 100044, China; (M.Z.); (S.L.)
| | - Shuolei Li
- Department of Animal Laboratory, Peking University People’s Hospital, Beijing 100044, China; (M.Z.); (S.L.)
| | - Yujing Chi
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China; (Y.Z.); (Q.Z.); (Z.W.); (N.C.)
- Department of Central Laboratory and Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China;
| | - Yulan Liu
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China; (Y.Z.); (Q.Z.); (Z.W.); (N.C.)
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
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19
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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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20
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Wang Z, Ling W, Wang T. A semiparametric quantile regression rank score test for zero-inflated data. Biometrics 2025; 81:ujaf050. [PMID: 40322848 PMCID: PMC12050976 DOI: 10.1093/biomtc/ujaf050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 02/26/2025] [Accepted: 04/04/2025] [Indexed: 05/08/2025]
Abstract
Zero-inflated data commonly arise in various fields, including economics, healthcare, and environmental sciences, where measurements frequently include an excess of zeros due to structural or sampling mechanisms. Traditional approaches, such as Zero-Inflated Poisson and Zero-Inflated Negative Binomial models, have been widely used to handle excess zeros in count data, but they rely on strong parametric assumptions that may not hold in complex real-world applications. In this paper, we propose a zero-inflated quantile single-index rank-score-based test (ZIQ-SIR) to detect associations between zero-inflated outcomes and covariates, particularly when nonlinear relationships are present. ZIQ-SIR offers a flexible, semi-parametric approach that accounts for the zero-inflated nature of the data and avoids the restrictive assumptions of traditional parametric models. Through simulations, we show that ZIQ-SIR outperforms existing methods by achieving higher power and better Type I error control, owing to its flexibility in modeling zero-inflated and overdispersed data. We apply our method to the real-world dataset: microbiome abundance from the Columbian Gut study. In this application, ZIQ-SIR identifies more significant associations than alternative approaches, while maintaining accurate type I error control.
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Affiliation(s)
- Zirui Wang
- Department of Statistics and Data Science, Tsinghua University, Beijing, 100084, China
| | - Wodan Ling
- Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, NY 10065, USA
| | - Tianying Wang
- Department of Statistics, Colorado State University, Fort Collins, CO 80523, USA
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21
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Chauhan G, Rieder F. The Pathogenesis of Inflammatory Bowel Diseases. Surg Clin North Am 2025; 105:201-215. [PMID: 40015812 PMCID: PMC11868724 DOI: 10.1016/j.suc.2024.10.008] [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] [Indexed: 03/01/2025]
Abstract
Inflammatory bowel diseases (IBDs) are relapsing, remitting inflammatory diseases of the intestinal tract. Familial aggregation and genome-wide association studies revealed susceptibility variants that point toward a combination of innate immune and adaptive immune dysregulation that in concert with environmental factors, such as our microbiome, can initiate and perpetuate inflammation. Innate immune perturbations include functional abnormalities in the intestinal barrier, endoplasmic reticulum stress, and abnormal recognition of microbes. Adaptive immune changes include dysregulation of cytokines, regulatory T cells, and leukocyte migration. IBD is linked with an abnormal wound-healing response leading to fibrosis. This article summarizes key pathogenic mechanisms in the pathogenesis of IBDs.
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Affiliation(s)
- Gaurav Chauhan
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Florian Rieder
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute; Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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22
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Kaden T, Alonso‐Román R, Stallhofer J, Gresnigt MS, Hube B, Mosig AS. Leveraging Organ-on-Chip Models to Investigate Host-Microbiota Dynamics and Targeted Therapies for Inflammatory Bowel Disease. Adv Healthc Mater 2025; 14:e2402756. [PMID: 39491534 PMCID: PMC12004439 DOI: 10.1002/adhm.202402756] [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: 07/25/2024] [Revised: 09/29/2024] [Indexed: 11/05/2024]
Abstract
Inflammatory bowel disease (IBD) is an idiopathic gastrointestinal disease with drastically increasing incidence rates. Due to its multifactorial etiology, a precise investigation of the pathogenesis is extremely difficult. Although reductionist cell culture models and more complex disease models in animals have clarified the understanding of individual disease mechanisms and contributing factors of IBD in the past, it remains challenging to bridge research and clinical practice. Conventional 2D cell culture models cannot replicate complex host-microbiota interactions and stable long-term microbial culture. Further, extrapolating data from animal models to patients remains challenging due to genetic and environmental diversity leading to differences in immune responses. Human intestine organ-on-chip (OoC) models have emerged as an alternative in vitro model approach to investigate IBD. OoC models not only recapitulate the human intestinal microenvironment more accurately than 2D cultures yet may also be advantageous for the identification of important disease-driving factors and pharmacological interventions targets due to the possibility of emulating different complexities. The predispositions and biological hallmarks of IBD focusing on host-microbiota interactions at the intestinal mucosal barrier are elucidated here. Additionally, the potential of OoCs to explore microbiota-related therapies and personalized medicine for IBD treatment is discussed.
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Affiliation(s)
- Tim Kaden
- Dynamic42 GmbH07745JenaGermany
- Institute of Biochemistry IICenter for Sepsis Control and CareJena University Hospital07747JenaGermany
| | - Raquel Alonso‐Román
- Department of Microbial Pathogenicity MechanismsLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
- Junior Research Group Adaptive Pathogenicity StrategiesLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
| | | | - Mark S. Gresnigt
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
- Junior Research Group Adaptive Pathogenicity StrategiesLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
| | - Bernhard Hube
- Department of Microbial Pathogenicity MechanismsLeibniz Institute for Natural Product Research and Infection Biology – Hans‐Knöll‐Institute07745JenaGermany
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
- Institute of MicrobiologyFaculty of Biological SciencesFriedrich Schiller University07743JenaGermany
| | - Alexander S. Mosig
- Institute of Biochemistry IICenter for Sepsis Control and CareJena University Hospital07747JenaGermany
- Cluster of Excellence Balance of the MicroverseFriedrich Schiller University Jena07745JenaGermany
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23
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Gilat R, Yazdi AA, Weissman AC, Joyce KM, Bouftas FA, Muth SA, Chisari E, Shohat N, Cole BJ. The Gut Microbiome and Joint Microbiome Show Alterations in Patients With Knee Osteoarthritis Versus Controls: A Systematic Review. Arthroscopy 2025; 41:1226-1238. [PMID: 38797504 DOI: 10.1016/j.arthro.2024.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 05/11/2024] [Indexed: 05/29/2024]
Abstract
PURPOSE To assess the current scientific literature on the microbiome's relation with knee osteoarthritis (OA), with specific focuses on the gut microbiome-joint axis and joint microbiome-joint axis. METHODS A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines; the PubMed, Embase, and Cochrane databases were searched for relevant English-language clinical studies on the gut and/or joint microbiomes' association with knee OA in humans. Bias was evaluated using the Methodological Index for Non-randomized Studies score. RESULTS Thirty-five thousand bacterial species comprise the gut microbiome; approximately 90% are members of the phyla Bacteroides and Firmicutes. Symbiosis between the gut microbiome and host under normal physiological conditions positively affects host growth, development, immunity, and longevity. Gut microbiome imbalance can negatively influence various physiological processes, including immune response, inflammation, metabolism, and joint health including the development of knee OA. In addition, next-generation gene sequencing suggests the presence of microorganisms in the synovial fluid of OA knees, and distinct microbiome profiles detected are presumed to play a role in the development of OA. Regarding the gut microbiome, consistent alterations in microbial composition between OA patients and controls are noted, in addition to several associations between certain gut bacteria and OA-related knee pain, patient-reported outcome measure performance, imaging findings, and changes in metabolic and inflammatory pathways. Regarding the joint microbiome, studies have revealed that increased levels of lipopolysaccharide and lipopolysaccharide-binding protein in synovial fluid are associated with activated macrophages-and are correlated with worsened osteophyte severity, joint space narrowing, and pain scores in knee OA patients. In addition, studies have shown various microbial composition differences in OA patients compared with controls, with certain joint microbes directly associated with OA pathogenesis, inflammation, and metabolic dysregulation. CONCLUSIONS The gut microbiome-joint axis and joint microbiome show alterations in microbial composition between patients with OA and controls. These alterations are associated with perturbations of metabolic and inflammatory pathways, imaging findings, OA-related pain, and patient-reported outcome measure performance. LEVEL OF EVIDENCE Level III, systematic review of Level II and III studies.
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Affiliation(s)
- Ron Gilat
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, U.S.A.; Department of Orthopaedic Surgery, Shamir Medical Center and Tel Aviv University, Tel Aviv, Israel
| | - Allen A Yazdi
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, U.S.A
| | - Alexander C Weissman
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, U.S.A
| | - Kaitlyn M Joyce
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, U.S.A
| | - Fatima A Bouftas
- The University of Chicago Pritzker School of Medicine, Chicago, Illinois, U.S.A
| | - Sarah A Muth
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, U.S.A
| | - Emanuele Chisari
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A
| | - Noam Shohat
- Department of Orthopaedic Surgery, Shamir Medical Center and Tel Aviv University, Tel Aviv, Israel
| | - Brian J Cole
- Midwest Orthopaedics at Rush University Medical Center, Chicago, Illinois, U.S.A..
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24
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Wei X, Tang D. Effect of Bacteroides on Crohn's disease. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:393-402. [PMID: 39586813 DOI: 10.1055/a-2435-2659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Crohn's disease (CD), also known as cicatrizing enteritis, is an inflammatory bowel disease that occurs in the distal ileum and right colon of unknown cause and is also called inflammatory bowel disease (IBD) with ulcerative colitis (UC). In recent years, intestinal biota have been confirmed to play a significant role in various gastrointestinal diseases. Studies have found that intestinal microbiota disorders are closely associated with the onset and progression of Crohn's disease. Bacteroidetes, the second largest microbiota in the intestine, are crucial for equilibrium in the microbiota and intestinal environment. Certain Bacteroides can induce the development of Crohn's disease and aggravate intestinal inflammation directly or through their metabolites. Conversely, certain Bacteroides can reduce intestinal inflammation and symptoms of Crohn's disease. This article reviews the effect of several intestinal Bacteroides in the onset and progression of Crohn's disease and their impact on its treatment.
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Affiliation(s)
- Xuanyu Wei
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China
| | - Dong Tang
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China
- Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital, Nanjing University, Yangzhou, China
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25
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Ahmadi A, Kouhsari E, Razavi S, Mohamadzadeh N, Besharat S, Vakili MA, Amiriani T. Comparative analysis of dominant gut microbiota in Inflammatory Bowel Disease patients and healthy individuals: A case-control study. New Microbes New Infect 2025; 64:101567. [PMID: 39991465 PMCID: PMC11846925 DOI: 10.1016/j.nmni.2025.101567] [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: 10/17/2024] [Revised: 01/24/2025] [Accepted: 02/03/2025] [Indexed: 02/25/2025] Open
Abstract
Background Chronic inflammation in the gut might be linked to microbiota dysbiosis. Objective This study aimed to investigate alterations in the gut microbiota composition of adult IBD patients compared to healthy controls. Methods This case-control study investigated the relationship between faecal microbiota composition and IBD in adults. Real-time qPCR analysis using bacterial 16S rRNA gene quantified the abundance of six key bacterial groups (Firmicutes, Lactobacillus spp., Bifidobacterium spp., Fusobacterium spp., Bacteroides fragilis, and Faecalibacterium prausnitzii) in faecal samples from 30 IBD patients (13 Crohn's disease, 17 ulcerative colitis) and 30 healthy controls. A correlation matrix was employed to assess relationships between these bacteria. Results Real-time qPCR revealed significant differences (p-value <0.05) in the abundance of several bacterial groups between IBD patients and healthy controls. Firmicutes, Fusobacterium spp., and B. fragilis were significantly more abundant (p-value <0.05) in IBD patients compared to controls. Conversely, Lactobacillus spp. and F. prausnitzii were both significantly less abundant (p-value <0.05) in IBD patients. While some bacterial groups exhibited trends toward higher abundance in either CD or UC patients, these differences were not statistically significant (p-value >0.111). The correlation matrix analysis revealed specific co-occurrence patterns: Bacteroides showed a strong negative correlation with Prevotella, more abundant in healthy controls, suggesting a shift in dominance in IBD patients. Lactobacillus spp. and F. prausnitzii exhibited a positive correlation in healthy individuals, indicating their potential cooperative role in maintaining gut homeostasis. Conclusion This study identified significant alterations in gut microbiota composition in adult IBD patients compared to healthy controls, with notable differences in the abundance of specific bacterial groups. These findings suggest that gut microbiota dysbiosis may play a critical role in IBD pathogenesis. The identification of specific bacterial imbalances provides a foundation for developing microbiota-based therapies, such as probiotics, prebiotics, and fecal microbiota transplantation, as potential interventions for restoring microbial balance and mitigating disease progression. Further research is needed to translate these insights into targeted therapeutic strategies and to explore their effectiveness in clinical settings.
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Affiliation(s)
- Alireza Ahmadi
- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
- Department of Laboratory Sciences, Faculty of Paramedicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ebrahim Kouhsari
- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
- Department of Laboratory Sciences, Faculty of Paramedicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Nima Mohamadzadeh
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Sima Besharat
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohammad Ali Vakili
- Health Management and Social Development Research Center, Department of Biostatistics and Epidemiology, Faculty of Health, Golestan University of Medical Sciences, Gorgan, Iran
| | - Taghi Amiriani
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
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26
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Chen Y, Liu N, Chen F, Liu M, Mu Y, Wang C, Xia L, Peng M, Zhou M. Alleviation effects of Lactobacillus plantarum in colitis aggravated by a high-salt diet depend on intestinal barrier protection, NF-κB pathway regulation, and oxidative stress improvement. Food Funct 2025; 16:2718-2736. [PMID: 40111251 DOI: 10.1039/d4fo06377e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
A high-salt diet (HSD) can result in numerous health issues, including exacerbation of intestinal inflammation. Therefore, there is an immediate necessity of developing dietary supplements that can mitigate colitis exacerbated by a HSD. This study examined the impact of Lactobacillus plantarum HGD228 on colitis exacerbated by a HSD and the mechanisms underlying its alleviation. HGD228 treatment significantly enhanced colonic goblet cells and MUC2, upregulated ZO-1 and occludin, inhibited epithelial cell apoptosis, and mitigated colitis exacerbated by a HSD. Moreover, HGD228 significantly regulated oxidative stress-related enzymes, including SOD, GSH-PX, and CAT. HGD228 treatment significantly suppressed the NF-κB pathway induced by a HSD and regulated the levels of cytokines, including TNF-α, IL-10, and IL-1β. Furthermore, HGD228 reestablished the gut microbiota altered by HSDDSS, increasing Bifidobacterium while decreasing Escherichia-Shigella and Clostridium sensu stricto 1. HGD228 treatment also enhanced the production of butyric acid and acetic acid, suppressed pro-inflammatory cytokines, and strengthened the intestinal mucosal barrier. Therefore, HGD228 enhanced the production of beneficial metabolites by regulating inflammatory cytokines and oxidative stress, preserving the mucosal barrier, and enhancing gut microbiota, and mitigated colitis aggravated by a HSD. These results will aid in clinical trials of probiotics and the development of dietary supplements for colitis, with promising application value.
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Affiliation(s)
- Yang Chen
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
| | - Nian Liu
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
| | - Fangyi Chen
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
| | - Mengyuan Liu
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
| | - Yang Mu
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
| | - Chao Wang
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
| | - Lusha Xia
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430068, China
| | - Mingye Peng
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
| | - Mengzhou Zhou
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
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27
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Sayed Y, Hassan M, Salem HM, Al-Amry K, Eid G. Probiotics/prebiotics effect on chicken gut microbiota and immunity in relation to heat-stress and climate-change mitigation. J Therm Biol 2025; 129:104097. [PMID: 40186955 DOI: 10.1016/j.jtherbio.2025.104097] [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: 09/18/2024] [Revised: 02/07/2025] [Accepted: 03/14/2025] [Indexed: 04/07/2025]
Abstract
Heat stress is a serious hazard that threatens world poultry production. The avian gut microbiome plays a critical role in improving nutrient utilization, competing with pathogens, stimulating an immune response, and reducing inflammatory reactions. Hence, the gut microbiome has a positive impact on the host's health which appears in the shape of improved body weight, feed conversion rate, and increased birds' productivity (meat or eggs). Accordingly, this review shed light on the chicken gut microbiome, its correlation with the immunity of chicken, and how this affects the general health condition of the bird as well as, the role of prebiotics and probiotics in improving the gut health and increasing birds' productivity, especially under climate change and heat stress condition. The review aims to focus on the significance of maintaining healthy chickens in order to increase the production of poultry meat to satisfy human needs. A robust microbiota and a well-functioning immune system synergistically contribute to the optimal health and productivity of chickens.
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Affiliation(s)
- Yara Sayed
- Department of Microbiology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
| | - Mariam Hassan
- Department of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala City, 43511, Suez, Egypt; Department of Microbiology and Immunology, Faculty of Pharmacy Cairo University, Kasr El-Aini Street, Cairo, 11562, Cairo, Egypt.
| | - Heba M Salem
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; Department of Diseases of Birds, Rabbits, Fish & their Care & Wildlife, School of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Khaled Al-Amry
- Department of Microbiology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Gamal Eid
- Department of Microbiology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
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28
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Ribeiro NV, Anwar S, Withoff S, Jonkers IH. Shared Genetics in Celiac Disease and Inflammatory Bowel Disease Specify a Greater Role for Intestinal Epithelial Cells. Int J Mol Sci 2025; 26:2982. [PMID: 40243612 PMCID: PMC11988521 DOI: 10.3390/ijms26072982] [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: 02/05/2025] [Revised: 03/14/2025] [Accepted: 03/23/2025] [Indexed: 04/18/2025] Open
Abstract
The contribution of genetics to the development of gut-related autoimmune diseases such as celiac disease (CeD) and inflammatory bowel diseases (IBDs) is well-established, especially in immune cells, but pinpointing the significance of genetic variants to other cell types is more elusive. Increasing evidence indicates that intestinal epithelial cells are active players in modulating the immune response, suggesting that genetic variants affecting these cells could change cell behavior during disease. Moreover, fine-mapping genetic variants and causal genes to relevant cell types can help to identify drug targets and develop personalized targeted therapies. In this context, we reviewed the functions of genes in disease-associated loci shared by CeD and IBD that are expressed in epithelial cells and explored their potential impacts.
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Affiliation(s)
| | | | | | - Iris H. Jonkers
- Department of Genetics, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands; (N.V.R.); (S.A.); (S.W.)
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29
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Jiang Z, Li P, Qiu K, Liao Y, Chen X, Xuan J, Wang F, Ma H, Wang Y, Zhu M. Proteus mirabilis exacerbates ulcerative colitis by inhibiting mucin production. Front Microbiol 2025; 16:1556953. [PMID: 40201443 PMCID: PMC11975560 DOI: 10.3389/fmicb.2025.1556953] [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: 01/07/2025] [Accepted: 03/07/2025] [Indexed: 04/10/2025] Open
Abstract
Introduction Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration in colonic mucosa, accompanied by a defective epithelial barrier. Proteus mirabilis (P. mirabilis) bacterium is a putative intestinal pathogen with invasive ability, yet its role in UC inflammation and gut barrier disruption is unclear. This study aims to investigate its epidemiological presence, pathogenic roles and preventive strategy during UC inflammation. Method P. mirabilis culture and PCR amplification of the P. mirabilis-specific ureR gene were used to detect fecal P. mirabilis and determine its prevalence in UC and control stool specimens. P. mirabilis isolated from UC stool specimens was gavaged into dextran sulfate sodium (DSS)-treated mice. Inflammation and the mucus layer of colons were assessed through histological examination and cytokine quantification. Bacteriophages were screened and used to eliminate P. mirabilis in colitis animals. Results and discussion The fecal P. mirabilis bacteria were detected by PCR amplification of P. mirabilis-specific ureR gene. Of 41 UC patients, 65.9% patients were P. mirabilis positive, which was significantly higher than the controls. Administration of P. mirabilis aggravated DSS-induced colitis symptom and mucosal inflammation in mice. Interestingly, the colonic mucus layer, an essential component of the epithelial barrier, of the animals was dramatically disrupted, which was consistent with the alteration of human UC colon. The disrupted mucus layer was mediated by the down-regulation of IL-18 in intestinal epithelium. Importantly, a bacteriophage cocktail targeting P. mirabilis could restore the mucus barrier and alleviate the enteric inflammation. Thus, our results suggest that P. mirabilis is a UC pathobiont bacterium, which exacerbates the severity of UC inflammation owing to down-regulation of mucin production and IL-18 expression. Bacteriophage-mediated elimination of P. mirabilis may be effective in limiting UC inflammation.
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Affiliation(s)
- Zhihui Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
| | - Pengpeng Li
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
| | - Kehui Qiu
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
| | - Yang Liao
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
| | - Xin Chen
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
| | - Ji Xuan
- Department of Gastroenterology, Jinling Hospital, The Medical School of Nanjing University, Nanjing, China
| | - Fangyu Wang
- Department of Gastroenterology, Jinling Hospital, The Medical School of Nanjing University, Nanjing, China
| | - Hongfeng Ma
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
- Department of Rehabilitation Medicine, Huzhou Rehabilitation Hospital, Huzhou, China
| | - Ye Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
| | - Minsheng Zhu
- State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China
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Jin Y, Xu X, Huang K, Liang Z. Pre-Administration of Saccharomyces boulardii-Derived Postbiotics Effectively Prevents Dextran Sulfate Sodium-Induced Colitis in Mice. Foods 2025; 14:1109. [PMID: 40238198 PMCID: PMC11988871 DOI: 10.3390/foods14071109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/09/2025] [Accepted: 03/21/2025] [Indexed: 04/18/2025] Open
Abstract
Ulcerative colitis (UC) is effectively alleviated by Saccharomyces boulardii (S. boulardii), an important probiotic. Postbiotics, defined as beneficial non-viable microorganisms and/or their components, can potentially improve gut health. In this study, we utilized S. boulardii to prepare postbiotics via freeze-drying and spray-drying methods, characterized the resulting postbiotics, and investigated their efficacy and underlying mechanisms in preventing UC. In a mouse model of UC induced by dextran sulfate sodium (DSS), we found that prevention with two forms of S. boulardii postbiotics alleviated colitis symptoms triggered by DSS, mitigated colon tissue damage, maintained the distribution of intestinal occludin and ZO-1 proteins, and suppressed the secretion and expression of TNF-α, IL-1β, and IL-6 in serum and colon tissues. Additionally, S. boulardii postbiotics mitigated dysbiosis by modulating gut microbiota composition, including the balance between Bacteroidota and Firmicutes (F/B), as well as the levels of Akkermansia, Muribaculaceae, Dubosiella, and Turicibacter. In conclusion, as a novel biotherapeutic agent, S. boulardii postbiotics effectively prevent DSS-induced UC in mice. Compared to live S. boulardii, postbiotics may hold greater potential for UC prevention.
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Affiliation(s)
- Yuxin Jin
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.J.); (X.X.); (K.H.)
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xinge Xu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.J.); (X.X.); (K.H.)
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Kunlun Huang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.J.); (X.X.); (K.H.)
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Zhihong Liang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (Y.J.); (X.X.); (K.H.)
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
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31
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Alzahrani AJ, Al-Hebshi BM, Yahia ZA, Al-Judaibi EA, Alsaadi KH, Al-Judaibi AA. Impact of Microbiota Diversity on Inflammatory Bowel Disease. Microorganisms 2025; 13:710. [PMID: 40284547 PMCID: PMC12029714 DOI: 10.3390/microorganisms13040710] [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: 02/07/2025] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 04/29/2025] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition that includes two main types, Crohn's disease (CD) and ulcerative colitis (UC), involving inflammation of the gastrointestinal (GI) tract. The exact cause of IBD is unknown but could be a combination of genetic, environmental, and immune system factors. This study investigated the impact of IBD on microbiota diversity by evaluating the differences in microbial composition and the microbiota of a control group (A) of healthy individuals and a group (B) of IBD patients. Sixty biopsies were collected from participants recruited from hospitals in Makkah, Saudi Arabia. Biopsy specimens were taken during colonoscopy examination, and bacterial identification was performed by extracting ribosomal DNA from sigmoid colon biopsies using a DNeasy Blood & Tissue Kit. Metagenomics and bioinformatics analyses were then conducted to analyze and compare the microbiota in the two groups. The results showed that the varieties of core microbiome species were 3.81% greater in the IBD patients than in the members of the control group. Furthermore, the differences between the groups were significantly greater than the variations within each group. Differences between the two groups were detected in the relative abundance of Clostridium nexile, Ruminococcus gnavus, Ruminococcus faecis, and Escherichia coli. These results indicate that microbiota could play a role in the pathogenesis of IBD and suggest that microbial diversity can serve as a biomarker for diagnosing the disease and monitoring its progression.
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Affiliation(s)
- Ashwag J. Alzahrani
- Department of Biological Sciences, Microbiology Section, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.J.A.); (B.M.A.-H.); (E.A.A.-J.); (K.H.A.)
| | - Basma M. Al-Hebshi
- Department of Biological Sciences, Microbiology Section, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.J.A.); (B.M.A.-H.); (E.A.A.-J.); (K.H.A.)
| | - Zolfekar A. Yahia
- Department of Internal Medicine, Al Noor Specialist Hospital, Ministry of Health, Makkah 24242, Saudi Arabia;
| | - Effat A. Al-Judaibi
- Department of Biological Sciences, Microbiology Section, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.J.A.); (B.M.A.-H.); (E.A.A.-J.); (K.H.A.)
| | - Khloud H. Alsaadi
- Department of Biological Sciences, Microbiology Section, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.J.A.); (B.M.A.-H.); (E.A.A.-J.); (K.H.A.)
| | - Awatif A. Al-Judaibi
- Department of Biological Sciences, Microbiology Section, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia; (A.J.A.); (B.M.A.-H.); (E.A.A.-J.); (K.H.A.)
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32
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Lin YC, Pan YJ, Chang SM, Yang FY. Transcranial ultrasound stimulation ameliorates dextran sulphate sodium-induced colitis and behavioural disorders by suppressing the inflammatory response in the brain. Brain Commun 2025; 7:fcaf119. [PMID: 40170911 PMCID: PMC11957916 DOI: 10.1093/braincomms/fcaf119] [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: 11/21/2024] [Revised: 02/18/2025] [Accepted: 03/20/2025] [Indexed: 04/03/2025] Open
Abstract
Inflammatory bowel disease (IBD) is associated with neuroinflammation, which may contribute to an increased risk of neurodegenerative disorders. This research investigated the potential of transcranial low-intensity pulsed ultrasound (LIPUS) to mitigate colonic inflammation induced by dextran sulphate sodium (DSS), focusing on its effects via the brain-gut axis. Colitis and neuroinflammation were induced in mice by administering 3% (wt/vol) DSS for 7 days. Subsequently, the brain was subjected to LIPUS stimulation at intensities of 0.5 or 1.0 W/cm² for 3 days. Biological samples were analyzed using real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and histological observation. Behavioural dysfunctions were assessed using the open field test, novel object recognition task, and Y-maze test. The alteration in gut microbiota composition was assessed through 16S rRNA sequencing. LIPUS therapy notably alleviated colitis symptoms and suppressed inflammation in both the colon and hippocampus of DSS-exposed mice. Compared with the group treated only with DSS, the LIPUS treatment showed decreased crypt destruction and partial epithelial barrier preservation. Moreover, LIPUS preserved intestinal barrier function by upregulating the levels of occludin and zonula occludens, decreasing the levels of lipopolysaccharide (LPS) and LPS-binding protein in serum, and ameliorating behavioural disorders. Further analysis indicated that LIPUS did not significantly transform the composition of the intestinal microbiota, but the microbial community showed some differences from the community in the DSS-only treatment group. This study demonstrates that transcranial LIPUS stimulation could be a novel therapeutic strategy for IBD and neuroinflammation via regulation of inflammatory interactions across brain-gut axis.
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Affiliation(s)
- Yu-Chen Lin
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
| | - Yi-Ju Pan
- Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan City 320315, Taiwan
| | - Shu-Ming Chang
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
| | - Feng-Yi Yang
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
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33
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Hohmann M, Iliasov D, Larralde M, Johannes W, Janßen KP, Zeller G, Mascher T, Gulder TAM. Heterologous Expression of a Cryptic BGC from Bilophila sp. Provides Access to a Novel Family of Antibacterial Thiazoles. ACS Synth Biol 2025; 14:967-978. [PMID: 39999339 PMCID: PMC11934131 DOI: 10.1021/acssynbio.5c00042] [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: 01/15/2025] [Revised: 02/05/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025]
Abstract
Human health is greatly influenced by the gut microbiota and microbiota imbalance can lead to the development of diseases. It is widely acknowledged that the interaction of bacteria within competitive ecosystems is influenced by their specialized metabolites, which act, e.g., as antibacterials or siderophores. However, our understanding of the occurrence and impact of such natural products in the human gut microbiome remains very limited. As arylthiazole siderophores are an emerging family of growth-promoting molecules in pathogenic bacteria, we analyzed a metagenomic data set from the human microbiome and thereby identified the bil-BGC, which originates from an uncultured Bilophila strain. Through gene synthesis and BGC assembly, heterologous expression and mutasynthetic experiments, we discovered the arylthiazole natural products bilothiazoles A-F. While established activities of related molecules indicate their involvement in metal-binding and -uptake, which could promote the growth of pathogenic strains, we also found antibiotic activity for some bilothiazoles. This is supported by biosensor-experiments, where bilothiazoles C and E show PrecA-suppressing activity, while bilothiazole F induces PblaZ, a biosensor characteristic for β-lactam antibiotics. These findings serve as a starting point for investigating the role of bilothiazoles in the pathogenicity of Bilophila species in the gut.
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Affiliation(s)
- Maximilian Hohmann
- Chair
of Technical Biochemistry, TUD Dresden University
of Technology, Bergstraße 66, 01069 Dresden, Germany
| | - Denis Iliasov
- General
Microbiology, TUD Dresden University of
Technology, Zellescher
Weg 20b, 01217 Dresden, Germany
| | - Martin Larralde
- Leiden
University Center for Infectious Diseases (LUCID), Leiden University Medical Center, 2333 ZA Leiden, Netherlands
| | - Widya Johannes
- Department
of Surgery, School of Medicine and Health, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Klaus-Peter Janßen
- Department
of Surgery, School of Medicine and Health, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany
| | - Georg Zeller
- Leiden
University Center for Infectious Diseases (LUCID) and Center for Microbiome
Analyses and Therapeutics (CMAT), Leiden
University Medical Center, 2333 ZA Leiden, Netherlands
| | - Thorsten Mascher
- General
Microbiology, TUD Dresden University of
Technology, Zellescher
Weg 20b, 01217 Dresden, Germany
| | - Tobias A. M. Gulder
- Chair
of Technical Biochemistry, TUD Dresden University
of Technology, Bergstraße 66, 01069 Dresden, Germany
- Department
of Natural Product Biotechnology, Helmholtz Institute for Pharmaceutical
Research Saarland (HIPS), Helmholtz Centre for Infection Research
(HZI) and Department of Pharmacy, PharmaScienceHub (PSH), Saarland University, Campus E8.1, 66123 Saarbrücken, Germany
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34
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Sun X, Zhai J. Research Status and Trends of Gut Microbiota and Intestinal Diseases Based on Bibliometrics. Microorganisms 2025; 13:673. [PMID: 40142565 PMCID: PMC11946491 DOI: 10.3390/microorganisms13030673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 02/27/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Gut microbiota plays an important role in gut health, and its dysbiosis is closely related to the pathogenesis of various intestinal diseases. The field of gut microbiota and intestinal diseases has not yet been systematically quantified through bibliometric methods. This study conducted bibliometric analysis to delineate the evolution of research on gut microbiota and intestinal diseases. Data were sourced from the Web of Science Core Collection database from 2009 to 2023 and were scientometrically analyzed using CiteSpace. We have found that the number of annual publications has been steadily increasing and showing an upward trend. China and the Chinese Academy of Sciences are the country and institution with the most contributions, respectively. Frontiers in Microbiology and Nutrients are the journals with the most publications, while Plos One and Nature are the journals with the most citations. The field has shifted from focusing on traditional descriptive analysis of gut microbiota composition to exploring the causal relationship between gut microbiota and intestinal diseases. The research hotspots and trends mainly include the correlation between specific intestinal diseases and gut microbiota diversity, the mechanism of gut microbiota involvement in intestinal diseases, the exploration of important gut microbiota related to intestinal diseases, and the relationship between gut microbiota and human gut health. This study provides a comprehensive knowledge map of gut microbiota and intestinal diseases, highlights key research areas, and outlines potential future directions.
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Affiliation(s)
- Xiao Sun
- Natural Reserve Planning and Research Institute, East China University of Technology, Nanchang 330013, China
- College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330029, China
| | - Jiancheng Zhai
- Natural Reserve Planning and Research Institute, East China University of Technology, Nanchang 330013, China
- School of Earth Sciences, East China University of Technology, Nanchang 330013, China
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Ramos C, Magistro D, Walton GE, Whitham A, Camp N, Poveda C, Gibson GR, Hough J, Kinnear W, Hunter K. Assessing the gut microbiota composition in older adults: connections to physical activity and healthy ageing. GeroScience 2025:10.1007/s11357-025-01605-w. [PMID: 40095191 DOI: 10.1007/s11357-025-01605-w] [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: 10/28/2024] [Accepted: 03/05/2025] [Indexed: 03/19/2025] Open
Abstract
The composition and functionality of the gut microbiota (GM) changes throughout the life course. As we move into older age, it starts to shift towards a less healthy one, which may lead to an imbalance in the GM community. Strategies that can reverse age-related dysbiosis are an important part of healthy aging. Little is known about the GM composition of older adults with different physical activity (PA) levels and whether it might contribute to healthy ageing. The aim of this study was to compare the GM composition of older adults with different PA levels and assess if it is associated with healthy ageing. 101 participants aged between 65-85 years undertook anthropometric measures, a 6-min walking test, wore an accelerometer for 7 days and provided a faecal sample. Faecal GM composition was analysed using 16S rRNA sequencing. We found that those who fulfilled the WHO/UK PA recommendations had higher relative abundance of several health-related bacteria such as Lactobacillus, F. prausnitzii and Roseburia intestinalis and lower abundance of disease-associated bacteria such as D.piger or Enterobacterales when compared to those who did not reach PA recommendations. These findings suggest that PA might improve the GM composition and has the potential to, at least partially, revert age-associated dysbiosis and promote healthy ageing.
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Affiliation(s)
- Catarina Ramos
- Department of Sport Science, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham, UK.
| | - Daniele Magistro
- Department of Sport Science, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham, UK
| | - Gemma E Walton
- Department of Food and Nutritional Sciences, The University of Reading, Whiteknights, Reading, UK
| | - Anya Whitham
- Department of Sport Science, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham, UK
| | - Nicola Camp
- Department of Sport Science, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham, UK
| | - Carlos Poveda
- Department of Food and Nutritional Sciences, The University of Reading, Whiteknights, Reading, UK
| | - Glenn R Gibson
- Department of Food and Nutritional Sciences, The University of Reading, Whiteknights, Reading, UK
| | - John Hough
- Department of Sport Science, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham, UK
| | - Will Kinnear
- Department of Sport Science, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham, UK
| | - Kirsty Hunter
- Department of Sport Science, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham, UK
- Reynolds Contamination Control, Lincoln, UK
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36
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Roy B, Cao K, Singh CO, Fang X, Yang H, Wei D. Advances in gut microbiota-related treatment strategies for managing colorectal cancer in humans. Cancer Biol Med 2025; 22:j.issn.2095-3941.2024.0263. [PMID: 40072039 PMCID: PMC11899591 DOI: 10.20892/j.issn.2095-3941.2024.0263] [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: 08/29/2024] [Accepted: 01/15/2025] [Indexed: 03/15/2025] Open
Abstract
Colorectal cancer (CRC) is a major contributor to global cancer-related mortality with increasing incidence rates in both developed and developing regions. Therefore, CRC presents a significant challenge to global health. The development of innovative tools for enhancing early CRC screening and diagnosis, along with novel treatments and therapies for improved management, remains an urgent necessity. CRC is intricately associated with the gut microbiota, which is integral to food digestion, nutrient generation, drug metabolism, metabolite production, immune enhancement, endocrine regulation, neurogenesis modulation, and the maintenance of physiologic and psychological equilibrium. Dysbiosis or imbalances in the gut microbiome have been implicated in various disorders, including CRC. Emerging evidence highlights the critical role of the gut microbiome in CRC pathogenesis and treatment, which presents potential opportunities for early detection and diagnosis. Despite substantial advances in understanding the relationship between the gut microbiota and CRC, significant challenges persist. Gaining a deeper and more detailed understanding of the interactions between the human microbiota and cancer is essential to fully realize the potential of the microbiota in cancer management. Unlike genetic factors, the gut microbiome is subject to modification, offering a promising avenue for the development of CRC treatments and drug discovery. This review provides an overview of the interactions between the human gut microbiome and CRC, while examining prospects for precision management of CRC.
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Affiliation(s)
- Bhaskar Roy
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Science, Hangzhou 310022, China
| | - Kunfeng Cao
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Science, Hangzhou 310022, China
- BGI Research, Shenzhen 518083, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | | | | | - Huanming Yang
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Science, Hangzhou 310022, China
- BGI Research, Shenzhen 518083, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
- James D. Watson Institute of Genome Sciences, Hangzhou 310029, China
| | - Dong Wei
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Science, Hangzhou 310022, China
- BGI Research, Shenzhen 518083, China
- Clin Lab, BGI Genomics, Beijing 100000, China
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37
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Loddo F, Laganà P, Rizzo CE, Calderone SM, Romeo B, Venuto R, Maisano D, Fedele F, Squeri R, Nicita A, Nirta A, Genovese G, Bartucciotto L, Genovese C. Intestinal Microbiota and Vaccinations: A Systematic Review of the Literature. Vaccines (Basel) 2025; 13:306. [PMID: 40266208 PMCID: PMC11946530 DOI: 10.3390/vaccines13030306] [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: 02/10/2025] [Revised: 03/04/2025] [Accepted: 03/05/2025] [Indexed: 04/24/2025] Open
Abstract
Background: Vaccination constitutes a low-cost, safe, and efficient public health measure that can help prevent the spread of infectious diseases and benefit the community. The fact that vaccination effectiveness varies among populations, and that the causes of this are still unclear, indicates that several factors are involved and should be thoroughly examined. The "intestinal microbiota" is the most crucial of these elements. Numerous clinical studies demonstrate the intestinal microbiota's significance in determining the alleged "immunogenicity" and efficacy of vaccines. This systematic review aimed to review all relevant scientific literature and highlight the role of intestinal microbiota in COVID-19, Salmonella typhi, Vibrio cholerae, and rotavirus vaccinations. Materials and Methods: The MESH terms "vaccines" and "microbiota" were used to search the major scientific databases PubMed, SciVerse Scopus, Web of Knowledge, and the Cochrane Central Register of Controlled Clinical Trials. Results: Between February 2024 and October 2024, the analysis was conducted using electronic databases, yielding a total of 235 references. Finally, 24 RCTs were chosen after meeting all inclusion criteria: eight studies of COVID-19, two studies of Salmonella typhi, three studies of Vibrio cholerae, and eleven studies of rotavirus. Only six of these demonstrated good study quality with a Jadad score of three or four. Conclusions: According to the review's results, the intestinal microbiota surely plays a role in vaccinations' enhanced immunogenicity, especially in younger people. As it is still unclear what mechanisms underlie this effect, more research is needed to better understand the role of the intestinal microbiota.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Giovanni Genovese
- Department of Biomedical, Dental and Morphological and Functional Imaging Sciences, University of Messina, 98122 Messina, Italy; (F.L.); (P.L.); (C.E.R.); (S.M.C.); (B.R.); (R.V.); (D.M.); (F.F.); (R.S.); (A.N.); (A.N.); (L.B.)
| | | | - Cristina Genovese
- Department of Biomedical, Dental and Morphological and Functional Imaging Sciences, University of Messina, 98122 Messina, Italy; (F.L.); (P.L.); (C.E.R.); (S.M.C.); (B.R.); (R.V.); (D.M.); (F.F.); (R.S.); (A.N.); (A.N.); (L.B.)
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Zeamer AL, Lai Y, Sanborn V, Loew E, Tracy M, Jo C, Ward DV, Bhattarai SK, Drake J, McCormick BA, Bucci V, Haran JP. Microbiome functional gene pathways predict cognitive performance in older adults with Alzheimer's disease. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.06.641911. [PMID: 40161798 PMCID: PMC11952313 DOI: 10.1101/2025.03.06.641911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Disturbances in the gut microbiome is increasing correlated with neurodegenerative disorders, including Alzheimer's Disease. The microbiome may in fact influence disease pathology in AD by triggering or potentiating systemic and neuroinflammation, thereby driving disease pathology along the "microbiota-gut-brain-axis". Currently, drivers of cognitive decline and symptomatic progression in AD remain unknown and understudied. Changes in gut microbiome composition may offer clues to potential systemic physiologic and neuropathologic changes that contribute to cognitive decline. Here, we recruited a cohort of 260 older adults (age 60+) living in the community and followed them over time, tracking objective measures of cognition, clinical information, and gut microbiomes. Subjects were classified as healthy controls or as having mild cognitive impairment based on cognitive performance. Those with a diagnosis of Alzheimer's Diseases with confirmed using serum biomarkers. Using metagenomic sequencing, we found that relative species abundances correlated well with cognition status (MCI or AD). Furthermore, gene pathways analyses suggest certain microbial metabolic pathways to either be correlated with cognitive decline or maintaining cognitive function. Specifically, genes involved in the urea cycle or production of methionine and cysteine predicted worse cognitive performance. Our study suggests that gut microbiome composition may predict AD cognitive performance.
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Affiliation(s)
- Abigail L. Zeamer
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Yushuan Lai
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | | | - Ethan Loew
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Matthew Tracy
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Cynthia Jo
- Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Doyle V. Ward
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Shakti K. Bhattarai
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | | | - Beth A. McCormick
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Vanni Bucci
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - John P. Haran
- Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
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Pai VV, Sarath AP, Kerkar Z. Gut microbiome in dermatology - A narrative review. Indian J Dermatol Venereol Leprol 2025; 0:1-11. [PMID: 40357977 DOI: 10.25259/ijdvl_1094_2024] [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: 07/22/2024] [Accepted: 12/08/2024] [Indexed: 05/15/2025]
Abstract
The gut microbiome and human body have co-evolved in a synergistic host-microbial relationship. The ideal composition of human gut microbiota is an elusive concept, but every individual has a unique gut microbiota profile with regional differences. Newer diagnostic techniques have helped identify different bacteria and their roles in health and disease. The gut microbiome composition is affected by various factors like age, diet, immune system, environmental factors, exercise, and drugs. The microbiome has varied roles in metabolism, immune response, immune tolerance and antimicrobial protection. Diet plays an important role in maintaining the gut microbial diversity. Loss of homoeostasis in the microbiome results in dysbiosis. Dysbiosis plays a role in many dermatological diseases like atopic dermatitis, psoriasis, acne, rosacea, hidradenitis suppurativa, connective tissue disorders and many other systemic conditions like obesity, diabetes, neurological disease and malignancy. Reconstitution of the gut microbiome ecology in the form of bacteriotherapy with the reintegration of certain strains of microbiota has a beneficial role in many of these disorders.
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Affiliation(s)
| | | | - Zenia Kerkar
- Department of Dermatology, Goa Medical College, Bambolim, India
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Malik S, Naqvi SAA, Shadali AH, Khan H, Christof M, Niu C, Schwartz DA, Adler DG. Fecal Microbiota Transplantation (FMT) and Clinical Outcomes Among Inflammatory Bowel Disease (IBD) Patients: An Umbrella Review. Dig Dis Sci 2025:10.1007/s10620-025-08946-8. [PMID: 40038211 DOI: 10.1007/s10620-025-08946-8] [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: 07/17/2024] [Accepted: 02/19/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND AND AIMS Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among patients with IBD. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in patients with IBD using published SRMAs. METHODS We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in patients with IBD. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in patients with IBD using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE. RESULTS Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty. CONCLUSION Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.
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Affiliation(s)
- Sheza Malik
- Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | | | | | - Hajra Khan
- Rawalpindi Medical College, Rawalpindi, Pakistan
| | | | - Chengu Niu
- Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | - David A Schwartz
- Gastroenterology and Hepatology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas G Adler
- Gastroenterology and Hepatology, Porter Adventist Hospital in Denver, Denver, CO, USA.
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41
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Lu X, Xv Y, Hu W, Sun B, Hu H. Targeting CD4+ T cells through gut microbiota: therapeutic potential of traditional Chinese medicine in inflammatory bowel disease. Front Cell Infect Microbiol 2025; 15:1557331. [PMID: 40099014 PMCID: PMC11911530 DOI: 10.3389/fcimb.2025.1557331] [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: 01/08/2025] [Accepted: 02/18/2025] [Indexed: 03/19/2025] Open
Abstract
Inflammatory Bowel Disease (IBD) is an autoimmune disease characterized by chronic relapsing inflammation of the intestinal tract. Gut microbiota (GM) and CD4+T cells are important in the development of IBD. A lot of studies have shown that GM and their metabolites like short-chain fatty acids, bile acids and tryptophan can be involved in the differentiation of CD4+T cells through various mechanisms, which in turn regulate the immune homeostasis of the IBD patients. Therefore, regulating CD4+T cells through GM may be a potential therapeutic direction for the treatment of IBD. Many studies have shown that Traditional Chinese Medicine (TCM) formulas and some herbal extracts can affect CD4+T cell differentiation by regulating GM and its metabolites. In this review, we mainly focus on the role of GM and their metabolites in regulating the differentiation of CD4+T cells and their correlation with IBD. We also summarize the current research progress on the regulation of this process by TCM.
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Affiliation(s)
- Xingyao Lu
- Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yichuan Xv
- Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Weiye Hu
- Department of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Boyun Sun
- Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongyi Hu
- Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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42
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Sharma M, Pudlo N, Järvå MA, Kaur A, John A, Burchill L, Lingford JP, Epa R, Abayakoon P, Scott NE, Turkenburg JP, Davies GJ, Martens EC, Goddard-Borger ED, Williams SJ. Sulfoglycolysis sustains Eubacterium rectale in low-fiber diets. J Biol Chem 2025; 301:108320. [PMID: 39956340 PMCID: PMC11968277 DOI: 10.1016/j.jbc.2025.108320] [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: 10/20/2024] [Revised: 02/09/2025] [Accepted: 02/12/2025] [Indexed: 02/18/2025] Open
Abstract
The production of short-chain fatty acids (SCFAs) by Firmicutes (Bacillota) within the human gastrointestinal tract is recognized as critical for gut health and the progression of a range of disease states. Firmicutes are the most diverse phylum of human gut bacteria, are highly studied, and are often specialized to degrade just a few polysaccharide substrates. Members of the Firmicutes include key bacteria that produce butyrate, an SCFA that is generally not produced by members of the other major phyla. Recently, it was shown that Eubacterium rectale, a widespread member of the Firmicutes belonging to the Clostridiales cluster XIVa, can grow on the unusual but ubiquitous plant-derived sugar SQ using a sulfoglycolytic sulfofructose transaldolase pathway. Here, we show that in addition to SQ, E. rectale can also grow on the SQ glycoside sulfoquinovosyl glycerol (SQGro). The 3D structure of the E. rectale sulfoquinovosidase (SftG) shares strong structural conservation with other carbohydrate-active enzyme family GH31 SQases. Using sequence-similarity networks, we provide new biological context to a conserved domain of unknown function protein SftX belonging to DUF4867, which is conserved in the sulfoglycolytic sulfofructose transaldolase pathway, and determine its 3D structure. Finally, with the aid of a synthetic mini-human microbiome reconstituted in germ-free mice, we show that an SQ dietary supplement can rescue E. rectale from population crashes that occur upon switching from a high-fiber to a low-fiber, high-fat diet. This suggests that SQ or SQGro has the potential as a prebiotic for promoting the maintenance of this important butyrate-producing bacterium within the colonic microbiota.
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Affiliation(s)
- Mahima Sharma
- York Structural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom
| | - Nicholas Pudlo
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Michael A Järvå
- ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
| | - Arashdeep Kaur
- School of Chemistry and Bio21 Molecular Science and Biotechnology Institute and University of Melbourne, Parkville, Victoria, Australia
| | - Alan John
- ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
| | - Laura Burchill
- School of Chemistry and Bio21 Molecular Science and Biotechnology Institute and University of Melbourne, Parkville, Victoria, Australia
| | - James P Lingford
- ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
| | - Ruwan Epa
- School of Chemistry and Bio21 Molecular Science and Biotechnology Institute and University of Melbourne, Parkville, Victoria, Australia
| | - Palika Abayakoon
- School of Chemistry and Bio21 Molecular Science and Biotechnology Institute and University of Melbourne, Parkville, Victoria, Australia
| | - Nichollas E Scott
- Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia
| | - Johan P Turkenburg
- York Structural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom
| | - Gideon J Davies
- York Structural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom.
| | - Eric C Martens
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
| | - Ethan D Goddard-Borger
- ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
| | - Spencer J Williams
- School of Chemistry and Bio21 Molecular Science and Biotechnology Institute and University of Melbourne, Parkville, Victoria, Australia.
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Hodgkiss R, Acharjee A. Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167618. [PMID: 39662756 DOI: 10.1016/j.bbadis.2024.167618] [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: 09/20/2024] [Revised: 11/20/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.
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Affiliation(s)
- Rebecca Hodgkiss
- College of Medicine and Health, Cancer and Genomic Sciences, University of Birmingham, B15 2TT Birmingham, UK
| | - Animesh Acharjee
- College of Medicine and Health, Cancer and Genomic Sciences, University of Birmingham, B15 2TT Birmingham, UK; Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, B15 2TT Birmingham, UK; MRC Health Data Research UK (HDR), Midlands Site, UK; Centre for Health Data Research, University of Birmingham, B15 2TT, UK.
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44
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Gao CY, Pan YJ, Su WS, Wu CY, Chang TY, Yang FY. Abdominal ultrasound stimulation alleviates DSS-induced colitis and behavioral disorders in mice by mediating the microbiota-gut-brain axis balance. Neurotherapeutics 2025; 22:e00494. [PMID: 39580323 PMCID: PMC12014354 DOI: 10.1016/j.neurot.2024.e00494] [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: 08/02/2024] [Revised: 10/17/2024] [Accepted: 11/14/2024] [Indexed: 11/25/2024] Open
Abstract
Inflammatory bowel disease (IBD) has the potential to induce neuroinflammation, which may increase the risk of developing neurodegenerative disorders. Ultrasound stimulation to the abdomen is a potential treatment for dextran sulfate sodium (DSS)-induced acute colitis. The present study aimed to investigate whether abdominal low-intensity pulsed ultrasound (LIPUS) can alleviate DSS-induced neuroinflammation through the microbiota-gut-brain axis. Male mice were fed DSS to induce ulcerative colitis. LIPUS stimulation was then applied to the abdomen at intensities of 0.5 and 1.0 W/cm2. Mouse biological samples were analyzed, and behavior was evaluated. [18F]FEPPA PET/CT imaging was employed to track and quantify inflammation in the abdomen and brain. Changes in the gut microbiota composition were analyzed using 16S rRNA sequencing. Abdominal LIPUS significantly inhibited the DSS-induced inflammatory response, repaired destroyed crypts, and partially preserved the epithelial barrier. [18F]FEPPA accumulation in the colitis-induced neuroinflammation in the abdomen and specific brain regions significantly decreased after LIPUS treatment. LIPUS maintained intestinal integrity by increasing zonula occludens and occludin levels, reduced lipopolysaccharide-binding protein and lipopolysaccharide levels in the serum, and improved behavioral dysfunctions. Moreover, LIPUS, at an intensity of 0.5 W/cm2, reshaped the gut microbiota in colitis-induced mice by increasing the relative abundance of the Firmicutes and decreasing the relative abundance of the Bacteroidota. Our findings demonstrated that abdominal LIPUS stimulation has the potential to be a novel therapeutic strategy to improve colitis-induced behavioral disorders through microbiota-gut-brain axis signaling.
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Affiliation(s)
- Cong-Yong Gao
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Ju Pan
- Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan City, Taiwan
| | - Wei-Shen Su
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Yi Wu
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ting-Yu Chang
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Feng-Yi Yang
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Hollinger MK, Grayson EM, Ferreira CM, Sperling AI. Harnessing the Farm Effect: Microbial Products for the Treatment and Prevention of Asthma Throughout Life. Immunol Rev 2025; 330:e70012. [PMID: 40035333 PMCID: PMC11877632 DOI: 10.1111/imr.70012] [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: 09/19/2024] [Accepted: 02/10/2025] [Indexed: 03/05/2025]
Abstract
It has long been appreciated that farm exposure early in life protects individuals from allergic asthma. Understanding what component(s) of this exposure is responsible for this protection is crucial to understanding allergic asthma pathogenesis and developing strategies to prevent or treat allergic asthma. In this review, we introduce the concept of Farm-Friends, or specific microbes associated with both a farm environment and protection from allergic asthma. We review the mechanism(s) by which these Farm-Friends suppress allergic inflammation, with a focus on the molecule(s) produced by these Farm-Friends. Finally, we discuss the relevance of Farm-Friend administration (oral vs. inhaled) for preventing the development and severity of allergic asthma throughout childhood and adulthood. By developing a fuller understanding of which Farm-Friends modulate host immunity, a greater wealth of prophylactic and therapeutic options becomes available to counter the current allergy epidemic.
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Affiliation(s)
- Maile K. Hollinger
- Beirne B. Carter Center for Immunology ResearchUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Emily M. Grayson
- Beirne B. Carter Center for Immunology ResearchUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Microbiology, Immunology, and Cancer BiologyUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Caroline M. Ferreira
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
- Institute of Environmental, Chemistry and Pharmaceutics Sciences, Department of Pharmaceutics SciencesFederal University of São PauloSão PauloBrazil
| | - Anne I. Sperling
- Beirne B. Carter Center for Immunology ResearchUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Microbiology, Immunology, and Cancer BiologyUniversity of VirginiaCharlottesvilleVirginiaUSA
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Li S, Zhuge A, Chen H, Han S, Shen J, Wang K, Xia J, Xia H, Jiang S, Wu Y, Li L. Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice. J Adv Res 2025; 69:413-426. [PMID: 38582300 PMCID: PMC11954817 DOI: 10.1016/j.jare.2024.03.026] [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: 11/29/2023] [Revised: 03/28/2024] [Accepted: 03/29/2024] [Indexed: 04/08/2024] Open
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear. OBJECTIVES In this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice. METHODS The mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed. RESULTS Sedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2. CONCLUSION Sedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.
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Affiliation(s)
- Shengjie Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Aoxiang Zhuge
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hui Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shengyi Han
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jian Shen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Kaicen Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jiafeng Xia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - He Xia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shiman Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Youhe Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, China.
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Zhuang J, Zhuang Z, Chen B, Yang Y, Chen H, Guan G. Odoribacter splanchnicus-derived extracellular vesicles alleviate inflammatory bowel disease by modulating gastrointestinal inflammation and intestinal barrier function via the NLRP3 inflammasome suppression. Mol Med 2025; 31:56. [PMID: 39934686 PMCID: PMC11816829 DOI: 10.1186/s10020-025-01063-2] [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: 08/29/2024] [Accepted: 01/02/2025] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Extracellular vesicles (EVs) derived from specific bacteria exert therapeutic potential on inflammatory diseases. Previous reports suggest the protective role of Odoribacter splanchnicus (O.splanchnicus) in inflammatory bowel disease (IBD). The effect of EVs derived from O.splanchnicus (Os-EVs) and the underlying mechanism on IBD were surveyed here. METHODS Os-EVs were derived with ultracentrifugation before characterization by transmission electron microscopy and nanoparticle tracking analysis. Based on IBD model mice induced by dextran sulfate sodium (DSS), the effects of Os-EVs on IBD symptoms, intestinal barrier dysfunction, and colonic apoptosis, inflammation as well as NLRP3 inflammasome activation were analyzed. NLRP3 knockout mice were exploited to judge the role of NLRP3 in Os-EVs against IBD. RESULTS Os-EVs were typically shaped as a double concave disc (average diameter = 95 nm). The administration of Os-EVs attenuated DSS-induced body weight loss, colon shortening, disease activity index score, and histological injury in mice. Os-EVs could also relieve intestinal barrier dysfunction and colonic apoptosis, as evidenced by the up-regulation of zona occludens-1 and Occludin and the decrease of TUNEL-positive staining in colonic tissues of IBD mice. Os-EVs downregulated the expression of the interleukin-1β (IL-1β), tumor necrosis factor-α, and IL-6, and elevated IL-10, accompanied by blockage of the NLRP3 inflammasome activation in DSS-induced mice. Furthermore, NLRP3 knockout mice experiments revealed that the protective role of Os-EVs in IBD relies on regulating NLRP3. CONCLUSION Our finding indicated that Os-EVs effectively ameliorated IBD through repressing NLRP3, strongly supporting the potential of probiotic-derived EVs for alleviating IBD.
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Affiliation(s)
- Jinfu Zhuang
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, 20th, Chazhong Road, Fuzhou, Fujian Province, 350005, P. R. China
| | - Zhicheng Zhuang
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, 20th, Chazhong Road, Fuzhou, Fujian Province, 350005, P. R. China
| | - Bin Chen
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, 20th, Chazhong Road, Fuzhou, Fujian Province, 350005, P. R. China
| | - Yuanfeng Yang
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, 20th, Chazhong Road, Fuzhou, Fujian Province, 350005, P. R. China
| | - Hengkai Chen
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, 20th, Chazhong Road, Fuzhou, Fujian Province, 350005, P. R. China.
| | - Guoxian Guan
- Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, 20th, Chazhong Road, Fuzhou, Fujian Province, 350005, P. R. China.
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Yu W, Sun S, Yan Y, Zhou H, Liu Z, Fu Q. The role of short-chain fatty acid in metabolic syndrome and its complications: focusing on immunity and inflammation. Front Immunol 2025; 16:1519925. [PMID: 39991152 PMCID: PMC11842938 DOI: 10.3389/fimmu.2025.1519925] [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: 10/30/2024] [Accepted: 01/09/2025] [Indexed: 02/25/2025] Open
Abstract
Metabolic syndrome (Mets) is an important contributor to morbidity and mortality in cardiovascular, liver, neurological, and reproductive diseases. Short-chain fatty acid (SCFA), an organismal energy donor, has recently been demonstrated in an increasing number of studies to be an important molecule in ameliorating immuno-inflammation, an important causative factor of Mets, and to improve lipid distribution, blood glucose, and body weight levels in animal models of Mets. This study reviews recent research advances on SCFA in Mets from an immune-inflammatory perspective, including complications dominated by chronic inflammation, as well as the fact that these findings also contribute to the understanding of the specific mechanisms by which gut flora metabolites contribute to metabolic processes in humans. This review proposes an emerging role for SCFA in the inflammatory Mets, followed by the identification of major ambiguities to further understand the anti-inflammatory potential of this substance in Mets. In addition, this study proposes novel strategies to modulate SCFA for the treatment of Mets that may help to mitigate the prognosis of Mets and its complications.
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Affiliation(s)
- Wenqian Yu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Siyuan Sun
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Yutong Yan
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Hong Zhou
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Ziyi Liu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Qiang Fu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Lin ZH, Li CP, Sun CK, Cho DY, Tsai FJ, Yip HT, Chang R, Hung YM. Increased Risk of Inflammatory Bowel Disease Among Patients With Nontyphoidal Salmonella Infections: A Population-Based Cohort Study. Inflamm Bowel Dis 2025; 31:351-361. [PMID: 38567440 DOI: 10.1093/ibd/izae053] [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: 09/06/2023] [Indexed: 04/04/2024]
Abstract
BACKGROUND Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD. METHODS Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation. RESULTS The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19). CONCLUSIONS Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.
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Affiliation(s)
- Zong-Han Lin
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chung-Pin Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Pancreatic Cancer, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Cheuk-Kwan Sun
- Department of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Der-Yang Cho
- Translational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Fuu-Jen Tsai
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan
- Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan
| | - Hei-Tung Yip
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Renin Chang
- Division of Medical Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yao-Min Hung
- Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital Taitung Branch, Taitung, Taiwan
- Master Program in Biomedicine, College of Science and Engineering, National Taitung University, Taitung, Taiwan
- College of Health and Nursing, Meiho University, Pingtung, Taiwan
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50
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Agudelo C, Kateete DP, Nasinghe E, Kamulegeya R, Lubega C, Mbabazi M, Baker N, Lin KY, Liu CC, Kasambula AS, Kigozi E, Komakech K, Mukisa J, Mulumba K, Mwachan P, Nakalanda BS, Nalubega GP, Nsubuga J, Sitenda D, Ssenfuka H, Cirolia GT, Gustafson JT, Wang R, Nsubuga ML, Yiga F, Stanley SA, Bagaya BS, Elliott A, Joloba M, Wolf AR. Enterococcus and Eggerthella species are enriched in the gut microbiomes of COVID-19 cases in Uganda. Gut Pathog 2025; 17:9. [PMID: 39905557 DOI: 10.1186/s13099-025-00678-4] [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: 09/11/2024] [Accepted: 01/02/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Infection with the COVID-19-causing pathogen SARS-CoV-2 is associated with disruption in the human gut microbiome. The gut microbiome enables protection against diverse pathogens and exhibits dysbiosis during infectious and autoimmune disease. Studies based in the United States and China have found that severe COVID-19 cases have altered gut microbiome composition when compared to mild COVID-19 cases. We present the first study to investigate the gut microbiome composition of COVID-19 cases in a population from Sub-Saharan Africa. Given the impact of geography and cultural traditions on microbiome composition, it is important to investigate the microbiome globally and not draw broad conclusions from homogenous populations. RESULTS We used stool samples in a Ugandan biobank collected from COVID-19 cases during 2020-2022. We profiled the gut microbiomes of 83 symptomatic individuals who tested positive for SARS-CoV-2 along with 43 household contacts who did not present any symptoms of COVID-19. The inclusion of healthy controls enables us to generate hypotheses about bacterial strains potentially related to susceptibility to COVID-19 disease, which is highly heterogeneous. Comparison of the COVID-19 patients and their household contacts revealed decreased alpha diversity and blooms of Enterococcus and Eggerthella in COVID-19 cases. CONCLUSIONS Our study finds that the microbiome of COVID-19 individuals is more likely to be disrupted, as indicated by decreased diversity and increased pathobiont levels. This is either a consequence of the disease or may indicate that certain microbiome states increase susceptibility to COVID-19 disease. Our findings enable comparison with cohorts previously published in the Global North, as well as support new hypotheses about the interaction between the gut microbiome and SARS-CoV-2 infection.
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Affiliation(s)
- Carolina Agudelo
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
| | - David Patrick Kateete
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Emmanuel Nasinghe
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Rogers Kamulegeya
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Christopher Lubega
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Monica Mbabazi
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Noah Baker
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
| | - Kathryn Y Lin
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
| | - Chang C Liu
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
| | - Arthur Shem Kasambula
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Edgar Kigozi
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Kevin Komakech
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - John Mukisa
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Kassim Mulumba
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Patricia Mwachan
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Brenda Sharon Nakalanda
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Gloria Patricia Nalubega
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Julius Nsubuga
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Diana Sitenda
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Henry Ssenfuka
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Giana T Cirolia
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
- Biophysics PhD Program, University of California, Berkeley, Berkeley, CA, USA
| | - Jeshua T Gustafson
- College of Engineering, University of California, Berkeley, Berkeley, CA, USA
| | - Ruohong Wang
- College of Engineering, University of California, Berkeley, Berkeley, CA, USA
| | - Moses Luutu Nsubuga
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Fahim Yiga
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Sarah A Stanley
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
- Department of Molecular Biology, University of California, Berkeley, Berkeley, CA, USA
| | - Bernard Ssentalo Bagaya
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda
| | - Alison Elliott
- MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
| | - Moses Joloba
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
- Integrated Biorepository of H3Africa Uganda (IBRH3AU), Kampala, Uganda.
| | - Ashley R Wolf
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
- Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
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