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1
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Lin W, Ruishi X, Caijiao X, Haoming L, Xuefeng H, Jiyou Y, Minqiang L, Shuo Z, Ming Z, Dongyang L, Xiaoxue F. Potential applications and mechanisms of natural products in mucosal-related diseases. Front Immunol 2025; 16:1594224. [PMID: 40370438 PMCID: PMC12075308 DOI: 10.3389/fimmu.2025.1594224] [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: 03/15/2025] [Accepted: 04/09/2025] [Indexed: 05/16/2025] Open
Abstract
The mucosal barrier serves as a crucial defense against external pathogens and allergens, being widely distributed across the respiratory, gastrointestinal, urogenital tracts, and oral cavity. Its disruption can lead to various diseases, including inflammatory bowel disease, asthma, urinary tract infections, and oral inflammation. Current mainstream treatments for mucosa-associated diseases primarily involve glucocorticoids and immunosuppressants, but their long-term use may cause adverse effects. Therefore, the development of safer and more effective therapeutic strategies has become a focus of research. Natural products, with their multi-target and multi-system regulatory advantages, offer a promising avenue for the treatment of mucosal diseases. This review summarizes the potential applications of natural products in diseases of mucosal barrier dysfunction through mechanisms such as immune modulation, inflammation inhibition, tight junction protein restoration, and gut microbiota regulation, with the aim of providing insights for the exploration of novel therapeutic strategies.
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Affiliation(s)
- Wang Lin
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xie Ruishi
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xu Caijiao
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Luo Haoming
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Hua Xuefeng
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Yao Jiyou
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Lu Minqiang
- The First People’s Hospital of Guangzhou, Department of Hepatobiliary and Pancreatic Surgery, Guangzhou, China
| | - Zhou Shuo
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Zhu Ming
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Li Dongyang
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Fang Xiaoxue
- Changchun University of Chinese Medicine, Changchun, China
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
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2
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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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3
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Xu Z, Lu H, Hu C, Wen Y, Shang D, Gan T, Guo Z, Dai L, Luo Y. Inulin alleviates chronic ketamine-induced impairments in memory and prepulse inhibition by regulating the gut microbiota, inflammation, and kynurenine pathway. Int J Biol Macromol 2025; 294:139503. [PMID: 39761880 DOI: 10.1016/j.ijbiomac.2025.139503] [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: 09/26/2024] [Revised: 12/14/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025]
Abstract
Chronic ketamine administration causes cognitive impairments similar to those observed in schizophrenia. Growing evidence suggests that patients with schizophrenia show alterations in gut microbiota, which is associated with cognitive impairments. Inulin could regulate gut microbiota. However, it is unclear whether chronic ketamine exposure causes cognitive impairments by mediating gut microbiota and whether inulin ameliorates these impairments. In this study, we found that chronic ketamine exposure for 14 days induced gut dysbiosis, thereby increasing gut permeability, upregulating LPS-activated TLR4-NF-κB-NLRP3 inflammatory pathway, causing hippocampal neuroinflammation and neuronal damage, activating tryptophan (TRP)-kynurenine (KYN)-kynurenic acid (KYNA) pathway in the hippocampus, peripheral serum, and feces, and thus leading to deficits in recognition memory and prepulse inhibition (PPI). In addition, inulin treatment restored gut dysbiosis by increasing the abundance of Turicibacter and Ileibacterium and decreasing the abundance of Alistipes, Alloprevotella, Desulfovibrio, and Parasutterella, which may improve gut barrier damage by upregulating tight junction protein expression, suppress LPS-mediated TLR4-NF-κB-NLRP3 inflammatory pathway to reduce neuroinflammation and neuronal damage, inhibit TRP-KYN-KYNA metabolism pathway, and thus alleviate chronic ketamine-associated impairments in PPI and memory. Our findings provide additional evidence that inulin treatment is a potential intervention strategy for treating chronic ketamine-associated cognitive impairments and cognitive deficits in schizophrenia.
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Affiliation(s)
- Zhilong Xu
- Institute of Neuropsychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Haoyang Lu
- Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Canrun Hu
- Institute of Neuropsychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Yuguan Wen
- Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Dewei Shang
- Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Tongying Gan
- Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Zhihao Guo
- Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Lijing Dai
- Department of Pharmacy, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China
| | - Yayan Luo
- Institute of Neuropsychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Liwan District, Guangzhou, Guangdong Province 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China.
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Ma G, Chen Z, Xie Z, Liu J, Xiao X. Mechanisms underlying changes in intestinal permeability during pregnancy and their implications for maternal and infant health. J Reprod Immunol 2025; 168:104423. [PMID: 39793281 DOI: 10.1016/j.jri.2025.104423] [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: 08/31/2024] [Revised: 12/01/2024] [Accepted: 01/03/2025] [Indexed: 01/13/2025]
Abstract
Proper regulation of intestinal permeability is essential for maintaining the integrity of the intestinal mucosal barrier. An abnormal increase in permeability can significantly contribute to the onset and progression of various diseases, including autoimmune disorders, metabolic conditions, allergies, and inflammatory bowel diseases. The potential connection between intestinal permeability and maternal health during pregnancy is increasingly recognized, yet a comprehensive review remains lacking. Pregnancy triggers a series of physiological structural adaptations and significant hormonal fluctuations that collectively contribute to an increase in intestinal permeability. Although an increase in intestinal permeability is typically a normal physiological response during pregnancy, an abnormal rise is associated with immune dysregulation, metabolic disorders, and various pregnancy-related complications, such as recurrent pregnancy loss, gestational diabetes mellitus, overweight and obesity during pregnancy, intrahepatic cholestasis of pregnancy, and preeclampsia. This paper discusses the components of the intestinal mucosal barrier, the concept of intestinal permeability and its measurement methods, and the mechanisms and physiological significance of increased intestinal permeability during pregnancy. It thoroughly explores the association between abnormal intestinal permeability during pregnancy and maternal diseases, aiming to provide evidence for the pathophysiology of disease development in pregnant women. Additionally, the paper examines intervention methods, such as gut microbiota modulation and nutritional interventions, to regulate intestinal permeability during pregnancy, improve immune and metabolic states, and offer feasible strategies for the prevention and adjuvant treatment of clinical pregnancy complications.
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Affiliation(s)
- Guangyu Ma
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Zhongsheng Chen
- Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China
| | - Zhuojun Xie
- General Medicine Department, Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, China
| | - JinXiang Liu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Xiaomin Xiao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
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5
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Macom RV, Brown CM. Gastrointestinal Dysfunction and Dysbiosis in Ischemic Stroke: Opportunities for Therapeutic Intervention. Pharmaceuticals (Basel) 2025; 18:320. [PMID: 40143100 PMCID: PMC11944649 DOI: 10.3390/ph18030320] [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: 11/11/2023] [Revised: 02/11/2025] [Accepted: 02/23/2025] [Indexed: 03/28/2025] Open
Abstract
Although strokes originate in the brain, it is now widely appreciated that peripheral organ systems are also impacted by stroke. The gastrointestinal system is one peripheral organ system that is impaired during ischemic stroke. This impairment results in numerous complications, which impede post-stroke recovery. Many of the gastrointestinal mechanisms that contribute to the pathophysiology of ischemic stroke remain poorly understood. This review will highlight the molecular and cellular mechanisms underlying gastrointestinal outcomes in stroke by focusing on the complex interactions that largely occur in the small intestine. The final portion of this review will focus on therapeutic interventions that target the gut as a strategy to prevent or delay functional impairment and cognitive disability in stroke patients.
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Affiliation(s)
- Rhiannon V. Macom
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506, USA;
| | - Candice M. Brown
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506, USA;
- Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Morgantown, WV 26506, USA
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6
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Koppula S, Wankhede N, Kyada A, Ballal S, Arya R, Singh AK, Gulati M, Sute A, Sarode S, Polshettiwar S, Marde V, Taksande B, Upaganlawar A, Fareed M, Umekar M, Kopalli SR, Kale M. The gut-brain axis: Unveiling the impact of xenobiotics on neurological health and disorders. Prog Neuropsychopharmacol Biol Psychiatry 2025; 136:111237. [PMID: 39732317 DOI: 10.1016/j.pnpbp.2024.111237] [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: 05/25/2024] [Revised: 11/12/2024] [Accepted: 12/23/2024] [Indexed: 12/30/2024]
Abstract
The Gut-Brain Axis (GBA) is a crucial link between the gut microbiota and the central nervous system. Xenobiotics, originating from diverse sources, play a significant role in shaping this interaction. This review examines how these compounds influence neurotransmitter dynamics within the GBA. Environmental pollutants can disrupt microbial populations, impacting neurotransmitter synthesis-especially serotonin, gamma-aminobutyric acid (GABA), and dopamine pathways. Such disruptions affect mood regulation, cognition, and overall neurological function. Xenobiotics also contribute to the pathophysiology of neurological disorders, with changes in serotonin levels linked to mood disorders and imbalances in GABA and dopamine associated with anxiety, stress, and reward pathway disorders. These alterations extend beyond the GBA, leading to complications in neurological health, including increased risk of neurodegenerative diseases due to neuroinflammation triggered by neurotransmitter imbalances. This review provides a comprehensive overview of how xenobiotics influence the GBA and their implications for neurological well-being.
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Affiliation(s)
- Sushruta Koppula
- College of Biomedical and Health Sciences, Konkuk University, Chungju-Si, Chungcheongbuk Do 27478, Republic of Korea
| | - Nitu Wankhede
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Ashishkumar Kyada
- Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Rajkot, -360003, Gujarat, India
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Renu Arya
- Department of Pharmacy, Chandigarh Pharmacy College, Chandigarh Group of Colleges-Jhanjeri, Mohali 140307, Punjab, India
| | | | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 1444411, India; ARCCIM, Faculty of Health, University of Technology Sydney, Ultimo, NSW 20227, Australia
| | - Astha Sute
- National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India
| | - Sanskruti Sarode
- National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India
| | - Shruti Polshettiwar
- National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India
| | - Vaibhav Marde
- Indian Institute of Technology (IIT), Hyderabad, Telangana 502284, India
| | - Brijesh Taksande
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Aman Upaganlawar
- SNJB's Shriman Sureshdada Jain College of Pharmacy, Neminagar, Chandwad, Nashik, Maharashtra, India
| | - Mohammad Fareed
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 11597, Saudi Arabia
| | - Milind Umekar
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India
| | - Spandana Rajendra Kopalli
- Department of Bioscience and Biotechnology, Sejong University, Gwangjin-gu, Seoul 05006, Republic of Korea
| | - Mayur Kale
- Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra 441002, India.
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7
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Lin CC, Chen CS. Bacterial proteome microarray technology in biomedical research. Trends Biotechnol 2025:S0167-7799(24)00361-5. [PMID: 39755450 DOI: 10.1016/j.tibtech.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 11/30/2024] [Accepted: 12/03/2024] [Indexed: 01/06/2025]
Abstract
Bacterial proteome microarrays are high-throughput, adaptable tools that allow the simultaneous investigation of thousands of proteins from various bacterial species. These arrays are used to explore bacterial pathogenicity, pathogen-host interactions, and clinical diseases. Recent advancements have expanded their application to profiling human antibodies, identifying biomarkers for infectious and autoimmune diseases, and studying antimicrobial peptides (AMPs). This review highlights significant outcomes from recent studies, focusing on their diverse applications in biomedical research. Notable findings include the identification of novel antigens and diagnostic markers for gastrointestinal infections, autoimmune diseases, and mental health disorders. This technology promises to further elucidate the complex relationship between bacteria and their hosts, ultimately informing the development of new diagnostic, therapeutic, and preventive strategies.
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Affiliation(s)
- Chia-Chi Lin
- School of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chien-Sheng Chen
- Department of Food Safety/Hygiene and Risk Management, National Cheng Kung University, Tainan, Taiwan; Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
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Sim EA, Kim SY, Kim S, Mun EG. Probiotic Potential and Enhanced Adhesion of Fermented Foods-Isolated Lactic Acid Bacteria to Intestinal Epithelial Caco-2 and HT-29 Cells. Microorganisms 2024; 13:32. [PMID: 39858799 PMCID: PMC11767436 DOI: 10.3390/microorganisms13010032] [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: 12/02/2024] [Revised: 12/24/2024] [Accepted: 12/25/2024] [Indexed: 01/27/2025] Open
Abstract
This study evaluated the probiotic potential of lactic acid bacteria (LAB) isolated from fermented milk and soymilk products purchased from local markets. The LAB strains were assessed for acid and bile resistance, antibiotic resistance, and adhesion to human intestinal epithelial models. Streptococcus thermophilus (JAMI_LB_02) and Lactiplantibacillus plantarum (JAMI_LB_05) showed the highest survival rates in artificial gastric and bile juices, at 87.17 ± 0.02% and 96.71 ± 4.10%, respectively, with all strains (except JAMI_LB_03) demonstrating antibiotic resistance. Adhesion ability indicated the superior performance of JAMI_LB_02 and JAMI_LB_05 compared to standard strains. JAMI_LB_02 adhered to Caco-2 cells at 2.10 ± 0.94% and to HT-29 cells at 3.32 ± 0.38%, exceeding standard strains (1.06 ± 0.13% and 1.89 ± 0.58%). JAMI_LB_05 achieved the highest rates at 5.62 ± 1.33% on Caco-2 and 5.76 ± 0.46% on HT-29 cells. Their combination (JAMI_LB_02 + JAMI_LB_05) significantly enhanced adhesion to 18.57 ± 5.49% on Caco-2 and 21.67 ± 8.19% on HT-29 cells, demonstrating strong synergy. These findings highlight the probiotic potential of the isolated LAB strains, particularly in mixed formulations, which may improve intestinal survival, adaptability, and efficacy. Further in vivo studies are warranted to validate their clinical applications and optimize strain combinations for human health benefits.
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Affiliation(s)
| | | | | | - Eun-Gyung Mun
- Jeonju AgroBio-Materials Institute (JAMI), Jeonju-si 54810, Republic of Korea; (E.A.S.)
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Wu B, Thant W, Bitman E, Liu T, Liu J, Paschalis EI, Xu KH, Nieman LT, Ting DT, Thimmiah N, Sun S, Abelman RO, Isakoff SJ, Spring LM, Bardia A, Ellisen LW. A TROP2/Claudin Program Mediates Immune Exclusion to Impede Checkpoint Blockade in Breast Cancer. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.12.02.626446. [PMID: 39677819 PMCID: PMC11642930 DOI: 10.1101/2024.12.02.626446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
Immune exclusion inhibits anti-tumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. Here, we demonstrate that Trophoblast Cell-Surface Antigen 2 (TROP2), a key target of emerging anti-cancer Antibody Drug Conjugates (ADCs), controls barrier-mediated immune exclusion in Triple-Negative Breast Cancer (TNBC) through Claudin 7 association and tight junction regulation. TROP2 expression is inversely correlated with T cell infiltration and strongly associated with outcomes in TNBC. Loss-of-function and reconstitution experiments demonstrate TROP2 is sufficient to drive tumor progression in vivo in a CD8 T cell-dependent manner, while its loss deregulates expression and localization of multiple tight junction proteins, enabling T cell infiltration. Employing a humanized TROP2 syngeneic TNBC model, we show that TROP2 targeting via hRS7, the antibody component of Sacituzumab govitecan (SG), enhances the anti-PD1 response associated with improved T cell accessibility and effector function. Correspondingly, TROP2 expression is highly associated with lack of response to anti-PD1 therapy in human breast cancer. Thus, TROP2 controls an immune exclusion program that can be targeted to enhance immunotherapy response.
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Affiliation(s)
- Bogang Wu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Win Thant
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Elena Bitman
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Ting Liu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Jie Liu
- Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA
| | | | - Katherine H. Xu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Linda T. Nieman
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - David T. Ting
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Nayana Thimmiah
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Sheng Sun
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Rachel O. Abelman
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Steven J. Isakoff
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Laura M. Spring
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Aditya Bardia
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
| | - Leif W. Ellisen
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
- Ludwig Center at Harvard, Boston, MA 02115, USA
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10
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Fass OZ, Clarke JO. Reflux, eosinophilic esophagitis, and celiac disease - the blurred lines. Curr Opin Otolaryngol Head Neck Surg 2024; 32:367-373. [PMID: 39513503 DOI: 10.1097/moo.0000000000000989] [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: 11/15/2024]
Abstract
PURPOSE OF REVIEW Gastroesophageal reflux disease (GERD) is a commonly recognized cause of dysphagia. Conversely, eosinophilic esophagitis (EoE) and celiac disease are rarer and often overlooked as dysphagia culprits. Overlap between these conditions complicates diagnosis and delays appropriate treatment. This review aims to clarify the distinctive dysphagia characteristics in each condition, explore potential overlaps, and offer guidance on differentiation. RECENT FINDINGS Recent studies have advanced our understanding of dysphagia mechanisms in GERD, EoE, and celiac disease, particularly in characterizing disordered motility and dysphagia's natural history. While upper endoscopy, biopsies, and manometry remain crucial in dysphagia assessment, novel diagnostic tools are emerging. New insights highlight the significance of cytokine-induced mucosal injury in all three conditions, revealing potential connections where mucosal damage in one disorder may contribute to the development of others. SUMMARY GERD, EoE, and celiac disease can coexist and present with similar symptoms. Distinguishing between them often entails upper endoscopy, esophageal biopsies, pH testing, and celiac serologies. EoE should be considered when GERD patients fail proton pump inhibitor therapy or when celiac patients have persistent esophageal symptoms despite a gluten-free diet. Consider celiac disease if dysphagia accompanies iron deficiency anemia, malabsorptive diarrhea, or osteoporosis. Recognizing the potential overlap between these conditions is crucial for guiding clinical evaluation and therapy.
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Affiliation(s)
- Ofer Z Fass
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA
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11
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Qi P, Chen X, Tian J, Zhong K, Qi Z, Li M, Xie X. The gut homeostasis-immune system axis: novel insights into rheumatoid arthritis pathogenesis and treatment. Front Immunol 2024; 15:1482214. [PMID: 39391302 PMCID: PMC11464316 DOI: 10.3389/fimmu.2024.1482214] [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: 08/17/2024] [Accepted: 09/09/2024] [Indexed: 10/12/2024] Open
Abstract
Rheumatoid arthritis is a widely prevalent autoimmune bone disease that imposes a significant burden on global healthcare systems due to its increasing incidence. In recent years, attention has focused on the interaction between gut homeostasis and the immune system, particularly in relation to bone health. Dysbiosis, which refers to an imbalance in the composition and function of the gut microbiota, has been shown to drive immune dysregulation through mechanisms such as the release of pro-inflammatory metabolites, increased gut permeability, and impaired regulatory T cell function. These factors collectively contribute to immune system imbalance, promoting the onset and progression of Rheumatoid arthritis. Dysbiosis induces both local and systemic inflammatory responses, activating key pro-inflammatory cytokines such as tumor necrosis factor-alpha, Interleukin-6, and Interleukin-17, which exacerbate joint inflammation and damage. Investigating the complex interactions between gut homeostasis and immune regulation in the context of Rheumatoid arthritis pathogenesis holds promise for identifying new therapeutic targets, revealing novel mechanisms of disease progression, and offering innovative strategies for clinical treatment.
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Affiliation(s)
- Peng Qi
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Xin Chen
- Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Jiexiang Tian
- Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Kexin Zhong
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Zhonghua Qi
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Menghan Li
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Xingwen Xie
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
- Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, China
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Vahidi Z, Saghi E, Mahmoudi M, RezaieYazdi Z, Esmaeili SA, Zemorshidi F, Samadi M, Rastin M. Lactobacillus rhamnosus and Lactobacillus delbrueckii Ameliorate the Expression of miR-125a and miR-146a in Systemic Lupus Erythematosus Patients. Appl Biochem Biotechnol 2024; 196:6330-6341. [PMID: 38351428 DOI: 10.1007/s12010-023-04827-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2023] [Indexed: 11/29/2024]
Abstract
The microRNAs are non-coding RNA molecules involved in physiological and pathological processes, causing autoimmune diseases such as systemic lupus erythematosus (SLE). Probiotics are living microorganisms that possess beneficial effects on the host immune system and modulate it. The effect of Lactobacillus rhamnosus and Lactobacillus delbrueckii on the expression of miR-125a and miR-146a was studied in peripheral blood mononuclear cells (PBMCs) from newly diagnosed lupus patients in this in vitro study. During this study, 20 recently diagnosed SLE patients and 20 healthy individuals participated. Ficoll method was used to isolate the PBMCs from whole blood, which were cultured for 48 h with Lactobacillus rhamnosus and Lactobacillus delbrueckii. In the next step, total RNA containing microRNA was extracted. cDNA was synthesized for miR-125a and miR-146a genes and analyzed by real-time PCR. Results were presented as fold changes. As compared to healthy controls, SLE patients expressed lower levels of miR-125a and miR-146a. PBMCs treated with Lactobacillus rhamnosus, Lactobacillus delbrueckii, or both probiotics had significantly higher levels of miR-125a and miR-146a compared to the untreated group. Treatment of PBMCs with both L. rhamnosus and L. delbrueckii upregulated the expression of miR-125a and miR-146a in treated cells compared with untreated cells in SLE patients (p = 0.02, p = 0.001). Lactobacillus rhamnosus and Lactobacillus delbrueckii modify lupus patients' immune responses and disease effects by regulating miR-125a and miR-146a.
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Affiliation(s)
- Zohreh Vahidi
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Effat Saghi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Mahmoudi
- Immunology Departments, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra RezaieYazdi
- Rheumatic Diseases Research Center, Ghaem Hospital, Internal Medicine Section, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed-Alireza Esmaeili
- Immunology Departments, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fariba Zemorshidi
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Morteza Samadi
- Department of Immunology, Faculty of Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Maryam Rastin
- Immunology Departments, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Mucientes A, Lisbona-Montañez JM, Mena-Vázquez N, Ruiz-Limón P, Manrique-Arija S, García-Studer A, Ortiz-Márquez F, Fernández-Nebro A. Intestinal Dysbiosis, Tight Junction Proteins, and Inflammation in Rheumatoid Arthritis Patients: A Cross-Sectional Study. Int J Mol Sci 2024; 25:8649. [PMID: 39201334 PMCID: PMC11354395 DOI: 10.3390/ijms25168649] [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: 07/05/2024] [Revised: 08/02/2024] [Accepted: 08/07/2024] [Indexed: 09/02/2024] Open
Abstract
Recent studies point to intestinal permeability as an important factor in the establishment and development of rheumatoid arthritis (RA). Tight junctions (TJs) play a major role in intestinal homeostasis. The alteration of this homeostasis is related to RA. Furthermore, RA patients present dysbiosis and a lower microbiota diversity compared to healthy individuals. A cross-sectional study including RA patients and sex- and age-matched healthy controls was performed. The quantification of TJ proteins was carried out by ELISA. Gut microbiota was evaluated by NGS platform Ion Torrent S. The inflammatory variables included were DAS28, CRP, inflammatory cytokines (IL-6, IL-1, TNF-α) and oxidised LDL. Claudin-1 levels showed significant differences between groups. Results evidenced a correlation between claudin-1 values and age (r: -0.293; p < 0.05), IL6 (r: -0.290; p < 0.05) and CRP (r: -0.327; p < 0.05), and between zonulin values and both age (r: 0.267; p < 0.05) and TNFα (r: 0.266; p < 0.05). Moreover, claudin-1 and CRP levels are related in RA patients (β: -0.619; p: 0.045), and in patients with high inflammatory activity, the abundance of the genus Veillonella is positively associated with claudin-1 levels (β: 39.000; p: 0.004).
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Affiliation(s)
- Arkaitz Mucientes
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
| | - José Manuel Lisbona-Montañez
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Málaga, Spain
| | - Natalia Mena-Vázquez
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
| | - Patricia Ruiz-Limón
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain
- CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain
| | - Sara Manrique-Arija
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Málaga, Spain
| | - Aimara García-Studer
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Málaga, Spain
| | - Fernando Ortiz-Márquez
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Málaga, Spain
| | - Antonio Fernández-Nebro
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, 29010 Málaga, Spain; (A.M.); (J.M.L.-M.); (P.R.-L.); (S.M.-A.); (A.G.-S.); (F.O.-M.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Málaga, Spain
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Kinashi Y, Tanaka K, Kimura S, Hirota M, Komiyama S, Shindo T, Hashiguchi A, Takahashi D, Shibata S, Karaki SI, Ohno H, Hase K. Intestinal epithelium dysfunctions cause IgA deposition in the kidney glomeruli of intestine-specific Ap1m2-deficient mice. EBioMedicine 2024; 106:105256. [PMID: 39059316 PMCID: PMC11338063 DOI: 10.1016/j.ebiom.2024.105256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 07/03/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Intestinal epithelial cells (IECs) serve as robust barriers against potentially hostile luminal antigens and commensal microbiota. Epithelial barrier dysfunction enhances intestinal permeability, leading to leaky gut syndrome (LGS) associated with autoimmune and chronic inflammatory disorders. However, a causal relationship between LGS and systemic disorders remains unclear. Ap1m2 encodes clathrin adaptor protein complex 1 subunit mu 2, which facilitates polarized protein trafficking toward the basolateral membrane and contributes to the establishment of epithelial barrier functions. METHODS We generated IEC-specific Ap1m2-deficient (Ap1m2ΔIEC) mice with low intestinal barrier integrity as an LSG model and examined the systemic impact. FINDINGS Ap1m2ΔIEC mice spontaneously developed IgA nephropathy (IgAN)-like features characterized by the deposition of IgA-IgG immune complexes and complement factors in the kidney glomeruli. Ap1m2 deficiency markedly enhanced aberrantly glycosylated IgA in the serum owing to downregulation and mis-sorting of polymeric immunoglobulin receptors in IECs. Furthermore, Ap1m2 deficiency caused intestinal dysbiosis by attenuating IL-22-STAT3 signaling. Intestinal dysbiosis contributed to the pathogenesis of IgAN because antibiotic treatment reduced aberrantly glycosylated IgA production and renal IgA deposition in Ap1m2ΔIEC mice. INTERPRETATION IEC barrier dysfunction and subsequent dysbiosis by AP-1B deficiency provoke IgA deposition in the mouse kidney. Our findings provide experimental evidence of a pathological link between LGS and IgAN. FUNDING AMED, AMED-CREST, JSPS Grants-in-Aid for Scientific Research, JST CREST, Fuji Foundation for Protein Research, and Keio University Program for the Advancement of Next Generation Research Projects.
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Affiliation(s)
- Yusuke Kinashi
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan
| | - Keisuke Tanaka
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan
| | - Shunsuke Kimura
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan.
| | - Masato Hirota
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan
| | - Seiga Komiyama
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan
| | - Tomoko Shindo
- Electron Microscope Laboratory, Keio University School of Medicine, Tokyo, Japan
| | - Akinori Hashiguchi
- Electron Microscope Laboratory, Keio University School of Medicine, Tokyo, Japan; Depatment of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Daisuke Takahashi
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan
| | - Shinsuke Shibata
- Electron Microscope Laboratory, Keio University School of Medicine, Tokyo, Japan; Division of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shin-Ichiro Karaki
- Laboratory of Physiology, Department of Environmental and Life Sciences, University of Shizuoka, Shizuoka, Japan
| | - Hiroshi Ohno
- RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan; Laboratory for Immune Regulation, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Koji Hase
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan; Institute of Fermentation Sciences (IFeS), Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan.
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15
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Ünal A, Ülfer G. Assessment of Serum Zonulin Levels in Individuals Diagnosed With Chronic Spontaneous Urticaria. Ann Dermatol 2024; 36:231-235. [PMID: 39082659 PMCID: PMC11291101 DOI: 10.5021/ad.24.020] [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: 02/06/2024] [Revised: 04/08/2024] [Accepted: 05/31/2024] [Indexed: 08/03/2024] Open
Abstract
BACKGROUND There have been reports indicating a correlation between heightened intestinal permeability and many autoimmune and chronic inflammatory disorders. The involvement of autoimmunity is now recognized as a significant factor in the development of chronic spontaneous urticaria (CSU). Zonulin is an important biomarker that regulates tight junction permeability within cells in the gastrointestinal tract, hence facilitating intestinal permeability. OBJECTIVE To evaluate the correlation of CSU with intestinal permeability by measuring the serum levels of zonulin in patients diagnosed with CSU. METHODS The study included 60 patients diagnosed with CSU and 64 age- and sex-matched healthy individuals as controls. Levels of serum zonulin were determined using the ELISA method. RESULTS Although the serum zonulin value of the patients was higher compared to the controls, the difference did not reach a significant level (24.65±8.49 ng/ml vs. 21.03±7.36 ng/ml, p=0.077). The serum zonulin level had a significant correlation with the urticaria activity score in the CSU group (p=0.013). The results of the current study revealed that serum zonulin values significantly differed between patients with CSU and healthy controls. CONCLUSION This study is important in terms of being the first to investigate the serum zonulin levels in CSU. However, there is a need for further studies with larger patient groups.
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Affiliation(s)
- Alkım Ünal
- Department of Dermatology, Medical Faculty, Istanbul Medipol University, Istanbul, Turkey.
| | - Gözde Ülfer
- Department of Biochemistry, Medical Faculty, Istanbul Medipol University, Istanbul, Turkey
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16
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Sapp PA, Townsend JR, Kirby TO, Govaert M, Duysburgh C, Verstrepen L, Marzorati M, Marshall TM, Esposito R. AG1 ®, a Novel Synbiotic, Maintains Gut Barrier Function following Inflammatory Challenge in a Caco-2/THP1-Blue™ Co-Culture Model. Microorganisms 2024; 12:1263. [PMID: 39065031 PMCID: PMC11278950 DOI: 10.3390/microorganisms12071263] [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: 05/13/2024] [Revised: 06/14/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Nutritional interventions to reduce gastrointestinal (GI) permeability are of significant interest to physically active adults and those experiencing chronic health conditions. This in vitro study was designed to assess the impact of AG1, a novel synbiotic, on GI permeability following an inflammatory challenge. Interventions [AG1 (vitamins/minerals, pre-/probiotics, and phytonutrients) and control (control medium)] were fed separately into a human GI tract model (stomach, small intestine, and colon). In the colonic phase, the GI contents were combined with fecal inocula from three healthy human donors. GI permeability was evaluated with transepithelial electrical resistance (TEER) in a Caco-2 (apical)/THP1-Blue™ (basolateral) co-culture model. The apical side received sodium butyrate (positive control) or Caco-2 complete medium (negative control) during baseline testing. In the 24 h experiment, the apical side received colonic simulation isolates from the GI model, and the basolateral side was treated with Caco-2 complete medium, then 6 h treatment with lipopolysaccharide. TEER was assessed at 0 h and 24 h, and inflammatory markers were measured at 30 h in triplicate. Paired samples t-tests were used to evaluate endpoint mean difference (MD) for AG1 vs. control. TEER was higher for AG1 (mean ± SD: 99.89 ± 1.32%) vs. control (mean ± SD: 92.87 ± 1.22%) following activated THP1-induced damage [MD: 7.0% (p < 0.05)]. AG1 maintained TEER similar to the level of the negative control [-0.1% (p = 0.02)]. No differences in inflammatory markers were observed. These in vitro data suggest that acute supplementation with AG1 might stimulate protective effects on GI permeability. These changes may be driven by SCFA production due to the pre-/probiotic properties of AG1, but more research is needed.
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Affiliation(s)
- Philip A. Sapp
- Research, Nutrition, and Innovation, AG1, Carson City, NV 89701, USA
| | - Jeremy R. Townsend
- Research, Nutrition, and Innovation, AG1, Carson City, NV 89701, USA
- Health & Human Performance, Concordia University Chicago, River Forest, IL 60305, USA
| | - Trevor O. Kirby
- Research, Nutrition, and Innovation, AG1, Carson City, NV 89701, USA
| | | | | | | | - Massimo Marzorati
- ProDigest BVBA, B-9052 Ghent, Belgium
- Center of Microbial Ecology and Technology (CMET), Ghent University, B-9000 Ghent, Belgium
| | - Tess M. Marshall
- Research, Nutrition, and Innovation, AG1, Carson City, NV 89701, USA
| | - Ralph Esposito
- Research, Nutrition, and Innovation, AG1, Carson City, NV 89701, USA
- Department of Nutrition, Food Studies, and Public Health, New York University-Steinhardt, New York, NY 10003, USA
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17
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Preuß B, Frank A, Terjung B, Spengler U, Berg C, Klein R. Autoantibodies to beta tubulin in autoimmune liver diseases-Relation to pANCA and clinical relevance. Clin Exp Immunol 2024; 216:146-158. [PMID: 37823420 PMCID: PMC11036111 DOI: 10.1093/cei/uxad114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 08/30/2023] [Accepted: 10/10/2023] [Indexed: 10/13/2023] Open
Abstract
There was evidence that perinuclear antineutrophil cytoplasmic antibodies (pANCA) in autoimmune liver diseases react with human beta-tubulin-5 (TBB5). Here, we reevaluate the specificity and clinical relevance of anti-TBB5 antibodies. Patients with untreated autoimmune hepatitis (AIH; n = 53), AIH under immunosuppressive therapy (AIH-IS; n = 125), primary sclerosing cholangitis (PSC; n = 40), primary biliary cholangitis (PBC; n = 250), nonautoimmune liver diseases (n = 158), inflammatory bowel diseases (IBD; n = 30), and healthy individuals (n = 62) were tested by enzyme-linked immunosorbent assay for IgG- and IgA-antibodies against recombinant human TBB5. pANCA were detected by immunofluorescence test. Sera were absorbed with TBB5 coupled to cyanogen bromide-activated sepharose. Prevalence and reactivity of IgG anti-TBB5 were significantly higher in patients with untreated AIH (68%; arbitrary units [AU] median: 369) than in PSC (28%; AU median: 84, P < 0.001), other liver diseases (14%; AU median: 185, P < 0.0001), IBD (3%; AU median: 111, P < 0.0001), and healthy controls (3%; AU median: 135; P < 0.0001). Anti-TBB5 did not correlate with pANCA, and immunoprecipitation with TBB5 did not abolish pANCA reactivity. In untreated AIH, anti-TBB5-reactivity was significantly higher than in AIH-IS. Transaminases decreased under IS preferentially in anti-TBB5-negative patients. There was no correlation between anti-TBB5-reactivity and histological stages. IgA-anti-TBB5 was mainly found in alcohol-associated liver disease (ALD; 39%). Our data do not support TBB5 as an autoantigenic target of pANCA. However, IgG-anti-TBB5 showed high specificity for (untreated) AIH. While they did not correlate with histological and laboratory parameters, their presence may indicate a poor response to IS.
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Affiliation(s)
- Beate Preuß
- Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University of Tuebingen, Tuebingen, Germany
| | - Amelie Frank
- Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University of Tuebingen, Tuebingen, Germany
| | - Birgit Terjung
- Department of Gastroenterology, GFO Kliniken Bonn, St. Josef Hospital, Bonn, Germany
| | - Ulrich Spengler
- Department of Gastroenterology and Hepatology, Nephrology, Infectious Diseases, Endocrinology and Diabetology, University of Bonn, Bonn, Germany
| | - Christoph Berg
- Department of Gastroenterology and Infectiology, University of Tuebingen, Tuebingen, Germany
| | - Reinhild Klein
- Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University of Tuebingen, Tuebingen, Germany
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Navarro-Ledesma S, Hamed-Hamed D, Pruimboom L. A new perspective of frozen shoulder pathology; the interplay between the brain and the immune system. Front Physiol 2024; 15:1248612. [PMID: 38617059 PMCID: PMC11009429 DOI: 10.3389/fphys.2024.1248612] [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: 06/27/2023] [Accepted: 03/18/2024] [Indexed: 04/16/2024] Open
Abstract
Frozen shoulder (FS), also known as adhesive capsulitis of the shoulder (FS), is a fibrotic inflammatory process of unknown etiology whose main symptoms are pain, stiffness and the loss of joint mobility. These symptoms may be associated with pathologies such as diabetes, Dupuytren's syndrome and the prevalence of today's sedentary lifestyle. This literature review provides an overview of the epidemiology and pathogenesis of this pathology, as well as the mechanisms of lowgrade chronic inflammation and infection, insulin resistance, and omics-science associated with it. We also propose a new hypothesis related to the possibility that the GABAergic system could play a decisive role in the development of frozen shoulder and that therefore diabetes type 1, endocrinological autoimmune disorders and frozen shoulder are connected by the same pathophysiological mechanisms. If that is true, the combined presence of psycho-emotional stress factors and pathogenic immune challenges could be the main causes of frozen shoulder syndrome. Finally, we propose a series of possible intervention strategies based on a multifactorial etiological and mechanistic concept.
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Affiliation(s)
- Santiago Navarro-Ledesma
- Department of Physical Therapy, Faculty of Health Sciences, Campus of Melilla, University of Granada, Melilla, Spain
- University Chair in Clinical Psychoneuroimmunology, University of Granada and PNI Europe, Melilla, Spain
| | - Dina Hamed-Hamed
- Clinical Medicine and Public Health PhD Program, Faculty of Health Sciences, University of Granada, Granada, Spain
| | - Leo Pruimboom
- University Chair in Clinical Psychoneuroimmunology, University of Granada and PNI Europe, Melilla, Spain
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19
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Pepe G, Corica D, Currò M, Aversa T, Alibrandi A, Ientile R, Caccamo D, Wasniewska M. Fasting and meal-related zonulin serum levels in a large cohort of obese children and adolescents. Front Endocrinol (Lausanne) 2024; 15:1329363. [PMID: 38405153 PMCID: PMC10885807 DOI: 10.3389/fendo.2024.1329363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 01/18/2024] [Indexed: 02/27/2024] Open
Abstract
Introduction Zonulin recently emerged as a valuable biological marker to assess the integrity of the intestinal mucosal barrier. Nevertheless, data about zonulin in pediatric age are extremely scarce. Aim of this study was to investigate the relationship between serum zonulin levels, both fasting and postprandial, with body mass index (BMI) and biochemical markers of insulin resistance (IR), insulin sensitivity, b-cell function and cardio-metabolic risk in obese non-diabetic youths. Methods One hundred and four children and adolescents with obesity (BMI ≥ 2.0 SDS) were enrolled (mean age 11.43 ± 2.66). All the patients underwent clinical and biochemical assessment, including oral glucose tolerance test (OGTT) and liver ultrasonography. Zonulin serum levels were measured at fasting state, at 60-minute and 120-minute OGTT timepoint. Results Impaired fasting glycaemia and impaired glucose tolerance were documented in 27.9% and 11.5% of patients, respectively. IR was documented in 69.2% of cases. Liver steatosis was diagnosed in 39.4%. Zonulin serum levels significantly increased from baseline to 60-minute and 120-minute OGTT timepoint (p positive correlation between BMI SDS and serum zonulin levels at 120-minute OGTT timepoint (p highlighted a positive association of zonulin fasting levels with IR and glutamicoxalacetic transaminase levels (GOT, p zonulin levels were demonstrated for age, sex, pubertal status, glucose, lipid profile and the other obesity-related parameters. Discussion Our results show, for the first time in a pediatric cohort, the meal-related pattern of secretion of serum zonulin, which tends to significantly increase during and at 2-hours postprandial assessment. Even if the underlying mechanisms associating intestinal permeability and obesity have not been fully elucidated yet, our data confirm a close relationship between zonulin concentration and obesity in pediatric population. IR seems to significantly influence zonulin serum levels, thus a central role of IR in this pathway is conceivable.
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Affiliation(s)
- Giorgia Pepe
- Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
| | - Domenico Corica
- Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
| | - Monica Currò
- Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
| | - Tommaso Aversa
- Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
| | | | - Riccardo Ientile
- Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
| | - Daniela Caccamo
- Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
| | - Malgorzata Wasniewska
- Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
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20
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Zhang J, Ren X, Wang S, Liu R, Shi B, Dong H, Wu Q. Microbial interventions in yak colibacillosis: Lactobacillus-mediated regulation of intestinal barrier. Front Cell Infect Microbiol 2024; 14:1337439. [PMID: 38390621 PMCID: PMC10883308 DOI: 10.3389/fcimb.2024.1337439] [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: 11/13/2023] [Accepted: 01/17/2024] [Indexed: 02/24/2024] Open
Abstract
Introduction The etiology of Escherichia coli in yaks, along with its drug resistance, results in economic losses within the yak breeding industry. The utilization of lactic acid bacteria treatment has emerged as a viable alternative to antibiotics in managing colibacillosis. Methods To elucidate the therapeutic mechanisms of Lactobacillus against Escherichia coli-induced intestinal barrier damage in yaks, we employed yak epithelial cells as the experimental model and established a monolayer epithelial barrier using Transwell. The study encompassed four groups: a control group, a model group (exposed to E. coli O78), a low-dose Lactobacillus group (E. coli O78 + 1 × 105CFU LAB), and a high-dose Lactobacillus group (E. coli O78 + 1 × 107CFU LAB). Various techniques, including transmembrane resistance measurement, CFU counting, RT-qPCR, and Western Blot, were employed to assess indicators related to cell barrier permeability and tight junction integrity. Results In the Model group, Escherichia coli O78 significantly compromised the permeability and tight junction integrity of the yak epithelial barrier. It resulted in decreased transmembrane resistance, elevated FD4 flux, and bacterial translocation. Furthermore, it downregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while upregulating the mRNA expression and protein expression of FABP2 and Zonulin, thereby impairing intestinal barrier function. Contrastingly, Lactobacillus exhibited a remarkable protective effect. It substantially increased transmembrane resistance, mitigated FD4 flux, and reduced bacterial translocation. Moreover, it significantly upregulated the mRNA and protein expression of MUC2, Occludin, and ZO-1, while downregulating the mRNA and protein expression of FABP2 and Zonulin. Notably, high-dose LAB demonstrated superior regulatory effects compared to the low-dose LAB group. Discussion In conclusion, our findings suggest that Lactobacillus holds promise in treating yak colibacillosis by enhancing mucin and tight junction protein expression. Furthermore, we propose that Lactobacillus achieves these effects through the regulation of Zonulin.
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Affiliation(s)
- Jingbo Zhang
- College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, China
| | - Xiaoli Ren
- College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, China
| | - Shuo Wang
- College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, China
| | - Ruidong Liu
- College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, China
| | - Bin Shi
- College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Autonomous Region Academy of Agriculture and Animal Science, Lhasa, China
| | - Hailong Dong
- College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, China
| | - Qingxia Wu
- College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, China
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21
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Gonçalves CL, Doifode T, Rezende VL, Costa MA, Rhoads JM, Soutullo CA. The many faces of microbiota-gut-brain axis in autism spectrum disorder. Life Sci 2024; 337:122357. [PMID: 38123016 DOI: 10.1016/j.lfs.2023.122357] [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: 09/20/2023] [Revised: 12/02/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.
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Affiliation(s)
- Cinara L Gonçalves
- Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
| | - Tejaswini Doifode
- Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health (UTHealth), Houston, TX, USA
| | - Victoria L Rezende
- Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - Maiara A Costa
- Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil
| | - J Marc Rhoads
- Department of Pediatrics, Division of Pediatric Gastroenterology, McGovern Medical School, The University of Texas Health (UTHealth), Houston, TX, USA
| | - Cesar A Soutullo
- Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health (UTHealth), Houston, TX, USA
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22
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Degirmencioglu Gok D, Tuygar Okutucu F, Ozturk N, Ceyhun HA. Association of bisphenol A with cognitive functions and functionality in adult attention deficit hyperactivity disorder. J Psychiatr Res 2024; 169:64-72. [PMID: 38000186 DOI: 10.1016/j.jpsychires.2023.11.027] [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: 05/29/2023] [Revised: 10/10/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Bisphenol A (BPA) has been linked to attention-deficit/hyperactivity disorder (ADHD) symptoms, but the effects on cognitive functions and functionality in adult ADHD have not been investigated. We investigated the associations between serum BPA with cognitive functions and functionality in adult ADHD patients. METHODS The levels of BPA were measured in 45 adult ADHD patients and 45 well-matched healty controls. The relationship between plastic exposure and BPA was also evaluated. Stroop test and Wisconsin Card Sorting Test were applied for neurocognitive evaluation and participants were compared in basic cognitive functions including planning, organization, abstraction, problem solving, strategy development, set shifting, cognitive flexibility, variants of attention, information processing speed, the ability to change perceptual setup and response under interference. Sheehan disability scale was applied for functionality. The association of BPA with test scores was analyzed statistically. RESULTS Serum BPA levels in adult ADHD patients were found to be significantly higher than in healthy controls. There was no relationship between plastic exposure and BPA levels. BPA levels showed a significant effect on functionality in terms of work field. There were significant differences between the groups in terms of cognitive functions. However, no significant correlation was found between BPA levels and cognitive functions. CONCLUSIONS BPA is associated with ADHD and affects functionality in the field of work, but larger-scale further studies are needed for its effect on cognitive functions.
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Affiliation(s)
| | | | - Nurinnisa Ozturk
- Department of Biochemistry, Ataturk University Medical Faculty, Erzurum, Turkey.
| | - Hacer Akgul Ceyhun
- Department of Psychiatry, Ataturk University Medical Faculty, Erzurum, Turkey.
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23
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Liu X, Liu M, Zhao M, Li P, Gao C, Fan X, Cai G, Lu Q, Chen X. Fecal microbiota transplantation for the management of autoimmune diseases: Potential mechanisms and challenges. J Autoimmun 2023; 141:103109. [PMID: 37690971 DOI: 10.1016/j.jaut.2023.103109] [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: 01/17/2023] [Revised: 08/17/2023] [Accepted: 08/28/2023] [Indexed: 09/12/2023]
Abstract
Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed.
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Affiliation(s)
- Xiaomin Liu
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China
| | - Mei Liu
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Ming Zhao
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China; Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, 421142, PR China
| | - Ping Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China
| | - Changxing Gao
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Xinyu Fan
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Guangyan Cai
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China.
| | - Qianjin Lu
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China; Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, 421142, PR China.
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China.
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24
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Diwan A, Harke SN, Panche AN. Host-microbiome interaction in fish and shellfish: An overview. FISH AND SHELLFISH IMMUNOLOGY REPORTS 2023; 4:100091. [PMID: 37091066 PMCID: PMC10113762 DOI: 10.1016/j.fsirep.2023.100091] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/28/2023] [Accepted: 03/30/2023] [Indexed: 04/03/2023] Open
Abstract
The importance of the gut microbiome in the management of various physiological activities including healthy growth and performance of fish and shellfish is now widely considered and being studied in detail for potential applications in aquaculture farming and the future growth of the fish industry. The gut microbiome in all animals including fish is associated with a number of beneficial functions for the host, such as stimulating optimal gastrointestinal development, producing and supplying vitamins to the host, and improving the host's nutrient uptake by providing additional enzymatic activities. Besides nutrient uptake, the gut microbiome is involved in strengthening the immune system and maintaining mucosal tolerance, enhancing the host's resilience against infectious diseases, and the production of anticarcinogenic and anti-inflammatory compounds. Because of its significant role, the gut microbiome is very often considered an "extra organ," as it plays a key role in intestinal development and regulation of other physiological functions. Recent studies suggest that the gut microbiome is involved in energy homeostasis by regulating feeding, digestive and metabolic processes, as well as the immune response. Consequently, deciphering gut microbiome dynamics in cultured fish and shellfish species will play an indispensable role in promoting animal health and aquaculture productivity. It is mentioned that the microbiome community available in the gut tract, particularly in the intestine acts as an innovative source of natural product discovery. The microbial communities that are associated with several marine organisms are the source of natural products with a diverse array of biological activities and as of today, more than 1000 new compounds have been reported from such microbial species. Exploration of such new ingredients from microbial species would create more opportunities for the development of the bio-pharma/aquaculture industries. Considering the important role of the microbiome in the whole life span of fish and shellfish, it is necessary to understand the interaction process between the host and microbial community. However, information pertaining to host-microbiome interaction, particularly at the cellular level, gene expression, metabolic pathways, and immunomodulation mechanisms, the available literature is scanty. It has been reported that there are three ways of interaction involving the host-microbe-environment operates to maintain homeostasis in the fish and shellfish gut i.e. host intrinsic factors, the environment that shapes the gut microbiome composition, and the core microbial community present in the gut system itself has equal influence on the host biology. In the present review, efforts have been made to collect comprehensive information on various aspects of host-microbiome interaction, particularly on the immune system and health maintenance, management of diseases, nutrient uptake, digestion and absorption, gene expression, and metabolism in fish and shellfish.
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Affiliation(s)
- A.D. Diwan
- Institute of Biosciences and Technology, Mahatma Gandhi Mission (MGM) University, Aurangabad, 431003, Maharashtra, India
| | - Sanjay N Harke
- Institute of Biosciences and Technology, Mahatma Gandhi Mission (MGM) University, Aurangabad, 431003, Maharashtra, India
| | - Archana N Panche
- Novo Nordisk Centre for Biosustainability, Technical University of Denmark, B220 Kemitorvet, 2800 Kgs, Lyngby, Denmark
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25
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Kharrazian D, Herbert M, Lambert J. The Relationships between Intestinal Permeability and Target Antibodies for a Spectrum of Autoimmune Diseases. Int J Mol Sci 2023; 24:16352. [PMID: 38003542 PMCID: PMC10671756 DOI: 10.3390/ijms242216352] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/09/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
The worldwide prevalence of autoimmune diseases that have limited treatment options and preventive strategies is rapidly rising. There is growing evidence that the microbiota and the integrity of the intestinal barrier play a role in autoimmune diseases. The potential to evaluate intestinal barrier integrity for susceptible individuals and to determine whether restoring intestinal junction integrity impacts autoimmune diseases is an important area of research that requires further attention. In the intestinal permeability model of autoimmune diseases, the breakdown of the intestinal tight junction proteins (zonulin/occludin) allows bacteria, toxins, undigested dietary proteins, and other antigens to pass into the lumen, thereby increasing the number of inflammatory reactions and the activation of immune cells throughout the body. In this study, we investigate the relationship between zonulin/occludin antibodies, which are used to determine intestinal permeability, with autoantibodies used to diagnose autoimmunity. Our investigation may identify significant levels of circulating autoantibodies in human subjects with intestinal permeability compared to those without intestinal permeability. Furthermore, we identified that significant positive linear correlations between serum occludin/zonulin antibodies and circulating autoantibodies could be used to determine autoimmune diseases.
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Affiliation(s)
- Datis Kharrazian
- Harvard Medical School, Boston, MA 02215, USA;
- Massachusetts General Hospital, Charlestown, MA 02114, USA
- Department of Preventive Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
| | - Martha Herbert
- Harvard Medical School, Boston, MA 02215, USA;
- Massachusetts General Hospital, Charlestown, MA 02114, USA
- Higher Synthesis Foundation, Cambridge, MA 02138, USA
| | - Jama Lambert
- Independent Researcher, Puerto Vallarta 48300, Jalisco, Mexico;
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26
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Khawar MM, Ijaz S, Goyal P, Kandambige D, Sharifa M, Maslamani ANJ, Al Kutabi S, Saleh I, Albshir MM, I Kh Almadhoun MK, Soomro SN, Kumari N. The Gut-Brain Axis in Autoimmune Diseases: Emerging Insights and Therapeutic Implications. Cureus 2023; 15:e48655. [PMID: 38090441 PMCID: PMC10712442 DOI: 10.7759/cureus.48655] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/07/2023] [Indexed: 05/04/2025] Open
Abstract
The gut-brain axis (GBA) is a two-way communication system that is influenced by signals from the nervous system, hormones, metabolism, the immune system, and microbes. The GBA may play a key role in gastrointestinal and neurological illnesses. Signaling events from the gut can regulate brain function. As a result, mounting data point to a connection between autoimmune disorders (AIDs), both neuroinflammatory and neurodegenerative diseases, and the GBA. Clinical, epidemiological, and experimental studies have shown that a variety of neurological illnesses are linked to alterations in the intestinal environment, which are suggestive of disease-mediated inter-organ communication between the gut and the brain. This review's objective is to draw attention to the clinical and biological relationship between the gut and the brain, as well as the clinical importance of this relationship for AIDs, neurodegeneration, and neuroinflammation. We also discuss the dysbiosis in the gut microbiota that has been linked to various AIDs, and we make some assumptions about how dietary changes such as prebiotics and probiotics may be able to prevent or treat AIDs by restoring the composition of the gut microbiota and regulating metabolites.
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Affiliation(s)
| | - Sami Ijaz
- Internal Medicine, North China University of Science & Technology, Tangshan, CHN
| | - Priya Goyal
- Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, IND
| | | | | | | | | | - Inam Saleh
- Pediatrics, University of Kentucky College of Medicine, Lexington, USA
| | | | | | | | - Neelam Kumari
- Internal Medicine, Jinnah Medical & Dental College, Karachi, PAK
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27
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Aboushaala K, Wong AYL, Barajas JN, Lim P, Al-Harthi L, Chee A, Forsyth CB, Oh CD, Toro SJ, Williams FMK, An HS, Samartzis D. The Human Microbiome and Its Role in Musculoskeletal Disorders. Genes (Basel) 2023; 14:1937. [PMID: 37895286 PMCID: PMC10606932 DOI: 10.3390/genes14101937] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/06/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023] Open
Abstract
Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immunological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs.
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Affiliation(s)
- Khaled Aboushaala
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
| | - Arnold Y. L. Wong
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China;
| | - Juan Nicolas Barajas
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
| | - Perry Lim
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
| | - Lena Al-Harthi
- Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA;
| | - Ana Chee
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
| | - Christopher B. Forsyth
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA;
| | - Chun-do Oh
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
| | - Sheila J. Toro
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
| | | | - Howard S. An
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
| | - Dino Samartzis
- Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA; (K.A.); (J.N.B.); (P.L.); (A.C.); (C.-d.O.); (S.J.T.); (H.S.A.)
- International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL 60612, USA
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Padilla N, Fabbri A, Della-Morte D, Ricordi C, Infante M. Papel inmunomodulador de la vitamina D y los ácidos grasos poliinsaturados omega-3 en trastornos autoinmunes: Revisión de la Literatura. ARCHIVOS LATINOAMERICANOS DE NUTRICIÓN 2023; 73:223-232. [DOI: 10.37527/2023.73.3.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
Los trastornos autoinmunes representan una familia de al menos 80 condiciones diferentes que surgen de una respuesta aberrante del sistema inmunológico resultando finalmente en la destrucción de tejidos y órganos específicos del cuerpo. Es importante destacar que durante las últimas tres décadas los estudios epidemiológicos han proporcionado evidencia de un aumento constante en la incidencia y prevalencia de trastornos autoinmunes. En los últimos años, varios estudios han demostrado que la vitamina D y los ácidos grasos poliinsaturados (AGPs) omega-3 ejercen propiedades inmunomoduladoras y antiinflamatorias sinérgicas que pueden aprovecharse positivamente para la prevención y el tratamiento de trastornos autoinmunes. En este sentido, el reciente ensayo clínico denominado VITAL (ensayo de vitamina D y omega 3); un estudio a gran escala, aleatorizado, doble ciego, controlado con placebo encontró que la suplementación conjunta de vitamina D y AGPs omega-3 (VIDOM) puede reducir la incidencia de enfermedades autoinmunes. En esta revisión de la literatura, resumimos los mecanismos moleculares detrás de las propiedades inmunomoduladoras y antiinflamatorias de la vitamina D y los AGPs omega-3, así como la posible interacción bidireccional entre el metabolismo de la vitamina D y el metabolismo de los AGPs omega-3 que justifica la co- suplementación VIDOM en trastornos autoinmunes.
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Faiyazuddin M, Sophia A, Ashique S, Gholap AD, Gowri S, Mohanto S, Karthikeyan C, Nag S, Hussain A, Akhtar MS, Bakht MA, Ahmed MG, Rustagi S, Rodriguez-Morales AJ, Salas-Matta LA, Mohanty A, Bonilla-Aldana DK, Sah R. Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review. Front Immunol 2023; 14:1264502. [PMID: 37818370 PMCID: PMC10561264 DOI: 10.3389/fimmu.2023.1264502] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 09/11/2023] [Indexed: 10/12/2023] Open
Abstract
The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk.
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Affiliation(s)
- Md. Faiyazuddin
- School of Pharmacy, Al – Karim University, Katihar, Bihar, India
- Nano Drug Delivery®, Raleigh-Durham, NC, United States
| | - A. Sophia
- PG & Research Department of Physics, Cauvery College for Women (Autonomous), Tiruchirappalli, Tamil Nadu, India
| | - Sumel Ashique
- Department of Pharmaceutics, Pandaveswar School of Pharmacy, Pandaveswar, West Bengal, India
| | - Amol D. Gholap
- Department of Pharmaceutics, St. John Institute of Pharmacy and Research, Palghar, Maharashtra, India
| | - S. Gowri
- PG & Research Department of Physics, Cauvery College for Women (Autonomous), Tiruchirappalli, Tamil Nadu, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - C. Karthikeyan
- Department of Chemical & Biochemical Engineering, Dongguk University, Seoul, Republic of Korea
| | - Sagnik Nag
- Department of Bio-Sciences, School of Biosciences & Technology (SBST), Vellore Institute of Technology (VIT), Tamil Nadu, India
| | - Arif Hussain
- School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates
| | - Mohammad Shabib Akhtar
- Department of Clinical Pharmacy, College of Pharmacy, Najran University, Najran, Saudi Arabia
| | - Md. Afroz Bakht
- Chemistry Department, College of Science and Humanity Studies, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Mohammed Gulzar Ahmed
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Alfonso J. Rodriguez-Morales
- Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas—Institución Universitaria Visión de las Américas, Pereira, Colombia
- Faculties of Health Sciences and Environmental Sciences, Universidad Científica del Sur, Lima, Peru
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
| | - Luis Andres Salas-Matta
- Faculties of Health Sciences and Environmental Sciences, Universidad Científica del Sur, Lima, Peru
| | - Aroop Mohanty
- Department of Clinical Microbiology, All India Institute of Medical Sciences, Gorakhpur, India
| | | | - Ranjit Sah
- Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
- Department of Clinical Microbiology, DY Patil Medical College, Hospital and Research Centre, DY Patil Vidyapeeth, Pune, Maharashtra, India
- Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha, India
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Hou M, Leng Y, Shi Y, Tan Z, Min X. Astragalus membranaceus as a Drug Candidate for Inflammatory Bowel Disease: The Preclinical Evidence. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2023; 51:1501-1526. [PMID: 37530507 DOI: 10.1142/s0192415x23500684] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/03/2023]
Abstract
Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that include Crohn's disease (CD) and ulcerative colitis (UC). Today, IBD has no successful treatment. As a result, it is of paramount importance to develop novel therapeutic agents for IBD prevention and treatment. Astragalus membranaceus (AMS) is a traditional Chinese medicine found in the AMS root. Modern pharmacological studies indicate that AMS and its constituents exhibit multiple bioactivities, such as anti-inflammatory, anti-oxidant, immune regulatory, anticancer, hypolipidemic, hypoglycemic, hepatoprotective, expectorant, and diuretic effects. AMS and its active constituents, which have been reported to be effective in IBD treatment, are believed to be viable candidate drugs for IBD treatment. These underlying mechanisms are associated with anti-inflammation, anti-oxidation, immunomodulation, intestinal epithelial repair, gut microbiota homeostasis, and improved energy metabolism. In this review, we summarize the efficacy and underlying mechanisms involved in IBD treatment with AMS and its active constituents in preclinical studies.
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Affiliation(s)
- Min Hou
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
| | - Yufang Leng
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
- Department of Anesthesiology, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
| | - Yajing Shi
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
| | - Zhiguo Tan
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
| | - Xiangzhen Min
- Department of Anesthesiology, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
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Justich MB, Rojas OL, Fasano A. The Role of Helicobacter pylori and Small Intestinal Bacterial Overgrowth in Parkinson's Disease. Semin Neurol 2023; 43:553-561. [PMID: 37562451 DOI: 10.1055/s-0043-1771468] [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: 08/12/2023]
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder whose etiology remains largely unexplained. Several studies have aimed to describe a causative effect in the interactions between the gastrointestinal tract and the brain, for both PD pathogenesis and disease course. However, the results have been controversial. Helicobacter pylori and small intestinal bacterial overgrowth (SIBO) are theorized to be agents capable of triggering chronic proinflammatory changes with a possible neurotoxic effect, as well as a cause of erratic L-dopa response in PD patients. This review evaluates the individual and possibly synergistic influence of H. pylori and SIBO on PD, to provide an opportunity to consider prospective therapeutic approaches.
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Affiliation(s)
- Maria Belen Justich
- Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
- Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Olga L Rojas
- Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada
- Department of Immunology, University of Toronto, Ontario, Canada
| | - Alfonso Fasano
- Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
- Division of Neurology, University of Toronto, Toronto, Ontario, Canada
- Department of Parkinson's Disease and Movement Disorders Rehabilitation, Moriggia-Pelascini Hospital - Gravedona ed Uniti, Como, Italy
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32
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Bertuccioli A, Cardinali M, Zonzini G, Neri M, Palazzi CM, Gregoretti A, Cazzaniga M, Di Pierro F. Clostridium butyricum Strain MIYAIRI 588 (CBM588) as a Precision Probiotic Therapy in the Ketogenic Diet: A Possible Application? MICROBIOLOGY RESEARCH 2023; 14:492-506. [DOI: 10.3390/microbiolres14020036] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
The ketogenic diet has proven to be effective in many recent studies not only as a weight-losing strategy but also as a valuable add-on therapy in medical conditions such as diabetes and epilepsy. Additionally, frequent conditions such as autism spectrum disorders and Alzheimer disease could have a benefit derived from ketogenic diet metabolic changes. Many of these benefits could be driven by an intestinal microbiota change. While the effects of a ketogenic diet on microbiota should still be thoroughly clarified, as most studies observe an increase in bacterial strains considered neuroprotective such as Akkermansia muciniphila, with a concomitant reduction in some pathogenic strains such as Salmonella spp. it is important to highlight how many studies show a reduction in butyrate-producing strains, leading to a colonic proinflammatory state with increased intestinal permeability and an increase in pathogenic bacterial strains. The Clostridium butyricum strain MIYAIRI 588 (CBM588) is a butyrate-producing strain that was recently approved for human use in Europe due to its safety and effectiveness. The beneficial effect of CBM588 on the human colon could derive from a mucosal layer thickness increase and mucosal immune cell regulation, leading to a reduction in diarrhea and mucosal damage. Additionally, CBM588 could improve systemic insulin sensitivity and reduce the splanchnic organ inflammatory state. Therefore, CBM588 is a bacterial strain that should be considered an add-on when following a ketogenic diet, leading to a reduction in some of the potential gastrointestinal side effects and improving weight management through increased insulin sensitivity and the optimization of the lipid metabolism.
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Affiliation(s)
- Alexander Bertuccioli
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61122 Urbino, Italy
| | - Marco Cardinali
- Department of Internal Medicine, Infermi Hospital, AUSL Romagna, 47921 Rimini, Italy
| | - Giordano Zonzini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61122 Urbino, Italy
| | - Marco Neri
- AIFeM Associazione Italiana Fitness e Medicina, 48121 Ravenna, Italy
| | | | - Aurora Gregoretti
- AIFeM Associazione Italiana Fitness e Medicina, 48121 Ravenna, Italy
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Arslan S, Altunisik N, Turkmen D, Uremis MM, Sener S, Turkoz Y. Evaluation of plasma zonulin level and its relationship with inflammatory cytokines in patients with vitiligo. J Cosmet Dermatol 2023; 22:1011-1016. [PMID: 36370419 DOI: 10.1111/jocd.15493] [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: 07/25/2022] [Revised: 10/18/2022] [Accepted: 10/21/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND It has been proven that there is an increase in intestinal permeability in some autoimmune diseases. In our study, we purposed to assess intestinal permeability in vitiligo disease by looking at zonulin levels. At the same time, we aimed to examine the correlation of inflammatory cytokines and lipopolysaccharide (LPS) levels with zonulin. METHODS Forty-one patients and 41 healthy participants were involved in our study. Blood samples were taken from all patients and controls, and the levels of zonulin, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and LPS were examined. RESULTS The mean of zonulin in the patient group was found to be statistically higher than the control group (p < 0.05). A positive correlation was found between zonulin level and IL-6, TNF-α, and LPS levels (p < 0.05). TNF-α and LPS levels in the vitiligo group were significantly higher than in the control group, but there was no such significance in terms of IL-6 levels. CONCLUSION We think that serum zonulin level increases and intestinal permeability increases in vitiligo disease.
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Affiliation(s)
- Selami Arslan
- Department of Dermatology, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Nihal Altunisik
- Department of Dermatology, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Dursun Turkmen
- Department of Dermatology, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Muhammed M Uremis
- Department of Biochemistry, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Serpil Sener
- Department of Dermatology, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Yusuf Turkoz
- Department of Biochemistry, Inonu University Faculty of Medicine, Malatya, Turkey
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Oteiza PI, Cremonini E, Fraga CG. Anthocyanin actions at the gastrointestinal tract: Relevance to their health benefits. Mol Aspects Med 2023; 89:101156. [PMID: 36379746 DOI: 10.1016/j.mam.2022.101156] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 11/15/2022]
Abstract
Anthocyanins (AC) are flavonoids abundant in the human diet, which consumption has been associated to several health benefits, including the mitigation of cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease, and neurological disorders. It is widely recognized that the gastrointestinal (GI) tract is not only central for food digestion but actively participates in the regulation of whole body physiology. Given that AC, and their metabolites reach high concentrations in the intestinal lumen after food consumption, their biological actions at the GI tract can in part explain their proposed local and systemic health benefits. In terms of mechanisms of action, AC have been found to: i) inhibit GI luminal enzymes that participate in the absorption of lipids and carbohydrates; ii) preserve intestinal barrier integrity and prevent endotoxemia, inflammation and oxidative stress; iii) sustain goblet cell number, immunological functions, and mucus production; iv) promote a healthy microbiota; v) be metabolized by the microbiota to AC metabolites which will be absorbed and have systemic effects; and vi) modulate the metabolism of GI-generated hormones. This review will summarize and discuss the latest information on AC actions at the GI tract and their relationship to overall health benefits.
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Affiliation(s)
- Patricia I Oteiza
- Department of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USA.
| | - Eleonora Cremonini
- Department of Nutrition, University of California, Davis, USA; Department of Environmental Toxicology, University of California, Davis, USA
| | - Cesar G Fraga
- Department of Nutrition, University of California, Davis, USA; Fisicoquímica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; Instituto de Bioquímica y Medicina Molecular (IBIMOL), UBA-CONICET, Buenos Aires, Argentina
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Huo J, Pei W, Liu G, Sun W, Wu J, Huang M, Lu W, Sun J, Sun B. Huangshui Polysaccharide Exerts Intestinal Barrier Protective Effects through the TLR4/MyD88/NF- κB and MAPK Signaling Pathways in Caco-2 Cells. Foods 2023; 12:foods12030450. [PMID: 36765977 PMCID: PMC9914309 DOI: 10.3390/foods12030450] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/09/2023] [Accepted: 01/14/2023] [Indexed: 01/20/2023] Open
Abstract
Several reports have demonstrated that natural polysaccharides exert protective effects on intestinal barrier function. In our previous study, we isolated a polysaccharide named HSP-W from Huangshui (HS). In the present study, the protective role of HSP-W in LPS-induced intestinal barrier dysfunction was determined by several molecular biological techniques. The results showed that HSP-W treatment alleviated the deduced TEER and increased the permeability of intestinal epithelial cells induced by LPS through inhibiting the release of inflammatory cytokines and enhancing the expression of tight junction (TJ) proteins. The underlying molecular mechanisms were elucidated by RNA-seq technique, which indicated that the differentially expressed genes (DEGs) between the LPS-treated and LPS+HSP-W-treated groups were enriched in the "MAPK" signaling pathway. Notably, the overlapping DEGs reversed by HSP-W intervention highlighted the pathways of the "Toll-like receptor" and "NF-κB" signaling pathways. The suppression of p38 and NF-κB were mediated by the inhibition of MyD88. Furthermore, HSP-W treatment prevented the translocation of NF-κB to nucleus, thus inhibiting the release of TNF-α, IL-6, and IL-1β. Overall, HSP-W has beneficial effects on LPS-induced inflammation; it protects the intestinal barrier from injury in Caco-2 cells through inhibiting the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways.
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Affiliation(s)
- Jiaying Huo
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
| | - Wenhao Pei
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
| | - Guoying Liu
- Anhui Gujing Distillery Co. Ltd., Bozhou 236820, China
| | - Weizheng Sun
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
| | - Jihong Wu
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
- Correspondence: ; Tel.: +86-156-5271-2036
| | - Mingquan Huang
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
| | - Wei Lu
- Anhui Gujing Distillery Co. Ltd., Bozhou 236820, China
| | - Jinyuan Sun
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
| | - Baoguo Sun
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
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Konno T, Martinez EE, Ji J, Miranda-Ribera A, Fiorentino MR, Fasano A. Human coagulation factor X and CD5 antigen-like are potential new members of the zonulin family proteins. Biochem Biophys Res Commun 2023; 638:127-133. [PMID: 36446155 PMCID: PMC9797450 DOI: 10.1016/j.bbrc.2022.11.047] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 11/15/2022] [Indexed: 11/18/2022]
Abstract
Zonulin is a physiologic epithelial and endothelial permeability modulator. Zonulin increases antigen trafficking from the gut lumen into the bloodstream and in between body compartments, a mechanism linked to many chronic inflammatory diseases. Upon its initial discovery, it was noted that zonulin was not a single protein, but rather a family of structurally and functionally related proteins referred to as the zonulin family proteins (ZFPs). ZFPs are members of the mannose associated serine proteases (MASP) family and are the result of high mutation rates leading to many zonulin polymorphisms. Pre-haptoglobin 2, the precursor of haptoglobin 2, was identified as the first eukaryotic member of the ZFPs, and properdin, a key positive regulator of the alternative pathway, as a second member. In this study, we report two additional proteins that are likely ZFPs. Human coagulation factor X (FX) and CD5 antigen-like (CD5L). Both FX and CD5L recombinant proteins were detected by anti-zonulin antibody in Western immunoblot analysis, and both proteins decreased epithelial barrier competency of Caco-2 cell monolayers as established by the Trans Epithelial Electrical Resistance (TEER) assay. These results indicate that FX and CD5L have structural and functional similarities with previously identified ZFPs and, therefore, can be considered new members of this family of proteins.
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Affiliation(s)
- Takumi Konno
- Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA, USA
| | - Enid E Martinez
- Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA, USA; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Jian Ji
- State Key Laboratory of Livestock and Poultry Breeding, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Alba Miranda-Ribera
- Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Maria R Fiorentino
- Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Alessio Fasano
- Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital-East, 16th Street, Building 114 (M/S 114-3503), Charlestown, MA, 02114-4404, USA.
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Asbjornsdottir B, Miranda-Ribera A, Fiorentino M, Konno T, Cetinbas M, Lan J, Sadreyev RI, Gudmundsson LS, Gottfredsson M, Lauth B, Birgisdottir BE, Fasano A. Prophylactic Effect of Bovine Colostrum on Intestinal Microbiota and Behavior in Wild-Type and Zonulin Transgenic Mice. Biomedicines 2022; 11:biomedicines11010091. [PMID: 36672598 PMCID: PMC9855927 DOI: 10.3390/biomedicines11010091] [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: 11/24/2022] [Revised: 12/22/2022] [Accepted: 12/26/2022] [Indexed: 12/31/2022] Open
Abstract
The microbiota-gut-brain axis (MGBA) involves bidirectional communication between intestinal microbiota and the gastrointestinal (GI) tract, central nervous system (CNS), neuroendocrine/neuroimmune systems, hypothalamic-pituitary-adrenal (HPA) axis, and enteric nervous system (ENS). The intestinal microbiota can influence host physiology and pathology. Dysbiosis involves the loss of beneficial microbial input or signal, diversity, and expansion of pathobionts, which can lead to loss of barrier function and increased intestinal permeability (IP). Colostrum, the first milk from mammals after birth, is a natural source of nutrients and is rich in oligosaccharides, immunoglobulins, growth factors, and anti-microbial components. The aim of this study was to investigate if bovine colostrum (BC) administration might modulate intestinal microbiota and, in turn, behavior in two mouse models, wild-type (WT) and Zonulin transgenic (Ztm)-the latter of which is characterized by dysbiotic microbiota, increased intestinal permeability, and mild hyperactivity-and to compare with control mice. Bioinformatics analysis of the microbiome showed that consumption of BC was associated with increased taxonomy abundance (p = 0.001) and diversity (p = 0.004) of potentially beneficial species in WT mice and shifted dysbiotic microbial community towards eubiosis in Ztm mice (p = 0.001). BC induced an anxiolytic effect in WT female mice compared with WT female control mice (p = 0.0003), and it reduced anxiogenic behavior in Ztm female mice compared with WT female control mice (p = 0.001), as well as in Ztm male mice compared with WT BC male mice (p = 0.03). As evidenced in MGBA interactions, BC supplementation may well be applied for prophylactic approaches in the future. Further research is needed to explore human interdependencies between intestinal microbiota, including eubiosis and pathobionts, and neuroinflammation, and the potential value of BC for human use. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).
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Affiliation(s)
- Birna Asbjornsdottir
- Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02152, USA
- School of Health Sciences, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
- Unit for Nutrition Research, Landspitali University Hospital and Faculty of Food Science and Nutrition, University of Iceland, 101 Reykjavik, Iceland
- Correspondence:
| | - Alba Miranda-Ribera
- Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02152, USA
| | - Maria Fiorentino
- Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02152, USA
| | - Takumi Konno
- Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02152, USA
| | - Murat Cetinbas
- Department of Molecular Biology and Pathology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Jinggang Lan
- Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02152, USA
| | - Ruslan I. Sadreyev
- Department of Molecular Biology and Pathology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Larus S. Gudmundsson
- School of Health Sciences, Faculty of Pharmaceutical Sciences, University of Iceland, 101 Reykjavik, Iceland
| | - Magnus Gottfredsson
- School of Health Sciences, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
- Department of Scientific Affairs, Landspitali University Hospital, 101 Reykjavik, Iceland
- Department of Infectious Diseases, Landspitali University Hospital, 101 Reykjavik, Iceland
| | - Bertrand Lauth
- School of Health Sciences, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
- Department of Child and Adolescent Psychiatry, Landspitali University Hospital, 105 Reykjavik, Iceland
| | - Bryndis Eva Birgisdottir
- Unit for Nutrition Research, Landspitali University Hospital and Faculty of Food Science and Nutrition, University of Iceland, 101 Reykjavik, Iceland
| | - Alessio Fasano
- Department of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02152, USA
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02114, USA
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Infantino C, Francavilla R, Vella A, Cenni S, Principi N, Strisciuglio C, Esposito S. Role of Vitamin D in Celiac Disease and Inflammatory Bowel Diseases. Nutrients 2022; 14:nu14235154. [PMID: 36501183 PMCID: PMC9735899 DOI: 10.3390/nu14235154] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/30/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Vitamin D (VD) is a pro-hormone that has long been known as a key regulator of calcium homeostasis and bone health in both children and adults. In recent years, studies have shown that VD may exert many extra-skeletal functions, mainly through a relevant modulation of the innate and adaptive immune system. This has suggested that VD could play a fundamental role in conditioning development, clinical course, and treatment of several autoimmune disorders, including celiac disease (CD) and inflammatory bowel diseases (IBDs). The main aim of this review is to evaluate the relationships between VD, CD, and IBDs. Literature analysis showed a potential impact of VD on CD and IBDs can be reasonably assumed based on the well-documented in vitro and in vivo VD activities on the gastrointestinal tract and the immune system. The evidence that VD can preserve intestinal mucosa from chemical and immunological damage and that VD modulation of the immune system functions can contrast the mechanisms that lead to the intestinal modifications characteristic of gastrointestinal autoimmune diseases has suggested that VD could play a role in controlling both the development and the course of CD and IBDs. Administration of VD in already diagnosed CD and IBD cases has not always significantly modified disease course. However, despite these relevant problems, most of the experts recommend monitoring of VD levels in patients with CD and IBDs and administration of supplements in patients with hypovitaminosis.
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Affiliation(s)
- Claudia Infantino
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
| | - Roberta Francavilla
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
| | - Adriana Vella
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
| | - Sabrina Cenni
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, 80138 Naples, Italy
| | | | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, 80138 Naples, Italy
| | - Susanna Esposito
- Department of Medicine and Surgery, Pediatric Clinic, University of Parma, 43126 Parma, Italy
- Correspondence: ; Tel.: +39-0521-704-790
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Chisari E, Cho J, Wouthuyzen-Bakker M, Parvizi J. Gut permeability may be associated with periprosthetic joint infection after total hip and knee arthroplasty. Sci Rep 2022; 12:15094. [PMID: 36064964 PMCID: PMC9445168 DOI: 10.1038/s41598-022-19034-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 08/23/2022] [Indexed: 12/24/2022] Open
Abstract
A growing number of recent investigations on the human genome, gut microbiome, and proteomics suggests that the loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. This cross-talk is highly influential in shaping the host immune system function and ultimately affecting the outcome of interventions. We hypothesized that the loss of mucosal barrier in the gut may be associatedto acute and chronic periprosthetic joint infections (PJI). Zonulin, soluble CD14 (sCD14), and lipopolysaccharide (LPS) were tested in plasma as part of a prospective cohort study of patients undergoing primary arthroplasty or revision arthroplasty because of an aseptic failure or PJI (as defined by the 2018 criteria). All blood samples were collected before antibiotic administration. Samples were tested using commercially available enzyme-linked immunosorbent assays as markers for gut permeability. A total of 134 patients were included in the study of which 44 patients had PJI (30 chronic and 14 acute), and the remaining 90 patients were categorized as non-infected that included 64 patients revised for aseptic failure, and 26 patients undergoing primary total joint arthroplasty. Both Zonulin (7.642 ± 6.077 ng/mL vs 4.560 ± 3.833 ng/mL; p < 0.001) and sCD14 levels (555.721 ± 216.659 ng/mL vs 396.872 ± 247.920 ng/mL; p = 0.003) were significantly elevated in the PJI group compared to non-infected cases. Higher levels of Zonulin were found in acute infections compared to chronic PJI (11.595 ± 6.722 ng/mL vs. 5.798 ± 4.841 ng/mL; p = 0.005). This prospective study reveals a possible link between gut permeability and the ‘gut-immune-joint axis’ in PJI. If this association continues to be borne out with a larger cohort and more in-depth analysis, it will have a clinically significant implication in managing patients with PJI. It may be that in addition to the administration of antimicrobials, patients with PJI and other orthopaedic infections may benefit from administration of gastrointestinal modulators such as pro and prebiotics.
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Affiliation(s)
- Emanuele Chisari
- Rothman Orthopaedic Institute at Thomas Jefferson University, 125 S 9th St. Ste 1000, Philadelphia, PA, 19107, USA. .,Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
| | - Jeongeun Cho
- Rothman Orthopaedic Institute at Thomas Jefferson University, 125 S 9th St. Ste 1000, Philadelphia, PA, 19107, USA
| | - Marjan Wouthuyzen-Bakker
- Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Javad Parvizi
- Rothman Orthopaedic Institute at Thomas Jefferson University, 125 S 9th St. Ste 1000, Philadelphia, PA, 19107, USA
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Charoensappakit A, Sae-Khow K, Leelahavanichkul A. Gut Barrier Damage and Gut Translocation of Pathogen Molecules in Lupus, an Impact of Innate Immunity (Macrophages and Neutrophils) in Autoimmune Disease. Int J Mol Sci 2022; 23:ijms23158223. [PMID: 35897790 PMCID: PMC9367802 DOI: 10.3390/ijms23158223] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 02/08/2023] Open
Abstract
The gut barrier is a single cell layer that separates gut micro-organisms from the host, and gut permeability defects result in the translocation of microbial molecules from the gut into the blood. Despite the silent clinical manifestation, gut translocation of microbial molecules can induce systemic inflammation that might be an endogenous exacerbating factor of systemic lupus erythematosus. In contrast, circulatory immune-complex deposition and the effect of medications on the gut, an organ with an extremely large surface area, of patients with active lupus might cause gut translocation of microbial molecules, which worsens lupus severity. Likewise, the imbalance of gut microbiota may initiate lupus and/or interfere with gut integrity which results in microbial translocation and lupus exacerbation. Moreover, immune hyper-responsiveness of innate immune cells (macrophages and neutrophils) is demonstrated in a lupus model from the loss of inhibitory Fc gamma receptor IIb (FcgRIIb), which induces prominent responses through the cross-link between activating-FcgRs and innate immune receptors. The immune hyper-responsiveness can cause cell death, especially apoptosis and neutrophil extracellular traps (NETosis), which possibly exacerbates lupus, partly through the enhanced exposure of the self-antigens. Leaky gut monitoring and treatments (such as probiotics) might be beneficial in lupus. Here, we discuss the current information on leaky gut in lupus.
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Affiliation(s)
- Awirut Charoensappakit
- Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kritsanawan Sae-Khow
- Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Asada Leelahavanichkul
- Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Nephrology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Rodrigues VF, Elias-Oliveira J, Pereira ÍS, Pereira JA, Barbosa SC, Machado MSG, Carlos D. Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front Immunol 2022; 13:934695. [PMID: 35874661 PMCID: PMC9300896 DOI: 10.3389/fimmu.2022.934695] [Citation(s) in RCA: 152] [Impact Index Per Article: 50.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 06/13/2022] [Indexed: 01/04/2023] Open
Abstract
Akkermansia muciniphila is a Gram-negative anaerobic mucus-layer-degrading bacterium that colonizes the intestinal mucosa of humans and rodents. Metagenomic data have shown an inverse correlation between the abundance of A. muciniphila and diseases such as inflammatory bowel disease (IBD), obesity, and diabetes. Thus, in recent decades, the potential of this bacterium as an immunomodulatory probiotic for autoimmune and chronic inflammatory diseases has been explored in experimental models. Corroborating these human correlation data, it has been reported that A. muciniphila slows down the development and progression of diabetes, obesity, and IBD in mice. Consequently, clinical studies with obese and diabetic patients are being performed, and the preliminary results are very promising. Therefore, this mini review highlights the main findings regarding the beneficial roles of A. muciniphila and its action mechanisms in autoimmune and chronic inflammatory diseases.
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Chancharoenthana W, Kamolratanakul S, Ariyanon W, Thanachartwet V, Phumratanaprapin W, Wilairatana P, Leelahavanichkul A. Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease. Front Cell Infect Microbiol 2022; 12:890817. [PMID: 35782108 PMCID: PMC9248029 DOI: 10.3389/fcimb.2022.890817] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 05/11/2022] [Indexed: 12/14/2022] Open
Abstract
Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.
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Affiliation(s)
- Wiwat Chancharoenthana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Tropical Immunology and Translational Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- *Correspondence: Wiwat Chancharoenthana, ; Asada Leelahavanichkul,
| | - Supitcha Kamolratanakul
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Tropical Immunology and Translational Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Wassawon Ariyanon
- Cardiometabolic Centre, Department of Medicine, Bangkok Nursing Hospital, Bangkok, Thailand
- Department of Medicine, Banphaeo General Hospital, Samutsakhon, Thailand
| | - Vipa Thanachartwet
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Weerapong Phumratanaprapin
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Asada Leelahavanichkul
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence on Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
- *Correspondence: Wiwat Chancharoenthana, ; Asada Leelahavanichkul,
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Li X, Yang B, Shi C, Wang H, Yu R, Li Q, Liu S. Synergistic Interaction of Low Salinity Stress With Vibrio Infection Causes Mass Mortalities in the Oyster by Inducing Host Microflora Imbalance and Immune Dysregulation. Front Immunol 2022; 13:859975. [PMID: 35663972 PMCID: PMC9162580 DOI: 10.3389/fimmu.2022.859975] [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: 01/22/2022] [Accepted: 04/19/2022] [Indexed: 11/13/2022] Open
Abstract
A sudden drop in salinity following extreme precipitation events usually causes mass mortality of oysters exposed to pathogens in ocean environment. While how low salinity stress interacts with pathogens to cause mass mortality remains obscure. In this study, we performed an experiment by low salinity stress and pathogen infection with Vibrio alginolyticus to investigate their synergistic effect on the mortality of the Pacific oyster toward understanding of the interaction among environment, host, and pathogen. We showed that low salinity stress did not significantly affect proliferation and virulence of V. alginolyticus, but significantly altered microbial composition and immune response of infected oysters. Microbial community profiling by 16S rRNA amplicon sequencing revealed disrupted homeostasis of digestive bacterial microbiota with the abundance of several pathogenic bacteria being increased, which may affect the pathogenesis in infected oysters. Transcriptome profiling of infected oysters revealed that a large number of genes associated with apoptosis and inflammation were significantly upregulated under low salinity, suggesting that low salinity stress may have triggered immune dysregulation in infected oysters. Our results suggest that host-pathogen interactions are strongly affected by low salinity stress, which is of great significance for assessing future environmental risk of pathogenic diseases, decoding the interaction among environment, host genetics and commensal microbes, and disease surveillance in the oyster.
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Affiliation(s)
- Xin Li
- Key Laboratory of Mariculture, Ministry of Education, and College of Fisheries, Ocean University of China, Qingdao, China
| | - Ben Yang
- Key Laboratory of Mariculture, Ministry of Education, and College of Fisheries, Ocean University of China, Qingdao, China
| | - Chenyu Shi
- Key Laboratory of Mariculture, Ministry of Education, and College of Fisheries, Ocean University of China, Qingdao, China
| | - Hebing Wang
- Key Laboratory of Mariculture, Ministry of Education, and College of Fisheries, Ocean University of China, Qingdao, China
| | - Ruihai Yu
- Key Laboratory of Mariculture, Ministry of Education, and College of Fisheries, Ocean University of China, Qingdao, China
| | - Qi Li
- Key Laboratory of Mariculture, Ministry of Education, and College of Fisheries, Ocean University of China, Qingdao, China.,Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Shikai Liu
- Key Laboratory of Mariculture, Ministry of Education, and College of Fisheries, Ocean University of China, Qingdao, China.,Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
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44
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Shaheen WA, Quraishi MN, Iqbal TH. Gut microbiome and autoimmune disorders. Clin Exp Immunol 2022; 209:161-174. [PMID: 35652460 DOI: 10.1093/cei/uxac057] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 04/29/2022] [Accepted: 05/30/2022] [Indexed: 12/13/2022] Open
Abstract
Autoimmune diseases have long been known to share a common pathogenesis involving a dysregulated immune system with failure to recognize self from non-self antigens. This immune dysregulation is now increasingly understood to be induced by environmental triggers in genetically predisposed individuals. Although several external environmental triggers have been defined in different autoimmune diseases, much attention is being paid to the role of the internal micro-environment occupied by the microbiome which was once termed "the forgotten organ". In this regard, the gut microbiome, serving as an intermediary between some of those external environmental effectors and the immune system helps programming of the immune system to be tolerant to innocent external and self antigens. However, in the presence of perturbed gut microbiota (dysbiosis), the immune system could be erroneously directed in favor of pro-inflammatory pathways to instigate different autoimmune processes. An accumulating body of evidence, including both experimental and human studies (observational and interventional) points to a role of gut microbiome in different autoimmune diseases. Such evidence could provide a rationale for gut microbiome manipulation with therapeutic and even preventative intents in patients with established or predisposed to autoimmune diseases respectively. Perturbations of the gut microbiome have been delineated in some immune mediated diseases, IBD in particular. However, such patterns of disturbance (microbiome signatures) and related pathogenetic roles of the gut microbiome are context dependent and cannot be generalized in the same exact way to other autoimmune disorders and the contribution of gut microbiome to different disease phenotypes has to be precisely defined. In this review, we revise the evidence for a role of gut microbiome in various autoimmune diseases and possible mechanisms mediating such a role.
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Affiliation(s)
- Walaa Abdelaty Shaheen
- University of Birmingham Microbiome Treatment Center, Birmingham, UK.,Institute of Cancer and Genomic Sciences, University of Birmingham, UK.,Gastroenterology Department, Menoufia University, Egypt
| | - Mohammed Nabil Quraishi
- University of Birmingham Microbiome Treatment Center, Birmingham, UK.,Institute of Cancer and Genomic Sciences, University of Birmingham, UK.,University Hospitals of Birmingham NHS Foundation Trust, Birmingham, UK
| | - Tariq H Iqbal
- University of Birmingham Microbiome Treatment Center, Birmingham, UK.,Institute of Microbiology and Infection, University of Birmingham, UK.,University Hospitals of Birmingham NHS Foundation Trust, Birmingham, UK
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45
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Wessels M, Auricchio R, Dolinsek J, Donat E, Gillett P, Mårild K, Meijer C, Popp A, Mearin ML. Review on pediatric coeliac disease from a clinical perspective. Eur J Pediatr 2022; 181:1785-1795. [PMID: 35034201 DOI: 10.1007/s00431-022-04379-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/05/2022] [Accepted: 01/06/2022] [Indexed: 12/19/2022]
Abstract
Coeliac disease is an immune-mediated condition characterized by chronic inflammation of the small bowel with villous atrophy driven by gluten ingestion in genetically predisposed individuals. It occurs frequently in both children and adults, affecting 1-4% of the population. The disease is associated with both gastrointestinal and extra-intestinal symptoms related to malabsorption and/or immune activation, and autoantibodies to tissue transglutaminase. Removal of gluten from the diet results in resolution of symptoms and enteropathy in the majority of patients. A good diagnostic work-up is important to avoid unnecessary restrictive diets in children. In this review on pediatric coeliac disease, we address epidemiology including predisposing environmental factors and possible preventive strategies, as well as the clinical presentation, diagnosis and follow-up. What is Known: •Primary prevention of coeliac disease is not possible; however, secondary prevention by targeting high-risk groups is recommended. •The diagnosis is safe without duodenal biopsies if specific conditions are met, also in asymptomatic children. What is New: •HLA-DQ typing is not routinely required for the diagnosis, whereas it can rule out coeliac disease if HLA-DQ2 and HLA-DQ8 are absent. •Follow-up could be improved by a more rational use of (laboratory) tests, increased intention to dietary compliance and quality of life.
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Affiliation(s)
- Margreet Wessels
- Department of Pediatrics, Rijnstate Hospital, Arnhem, the Netherlands.
| | - Renata Auricchio
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Jernej Dolinsek
- Department of Pediatrics, Hepatology and Nutrition Unit and Medical Faculty, Dept. of Pediatrics, University Medical Centre Maribor, GastroenterologyMaribor, Slovenia
| | - Ester Donat
- Pediatric Gastroenterology and Hepatology Unit, Celiac Disease and Digestive Immunopathology Unit, Hospital Universitari I Politècnic La Fe, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Peter Gillett
- Department of Pediatric Gastroenterology, Royal Hospital for Children and Young People, Scotland, Edinburgh, UK
| | - Karl Mårild
- Department of Pediatrics, Institute of Clinical Sciences, Department of Pediatric Gastroenterology, Sahlgrenska Academy, Queen Silvia Children's Hospital, Gothenburg, Sweden
| | - Caroline Meijer
- Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands
| | - Alina Popp
- University of Medicine and Pharmacy ''Carol Davila'', National Institute for Mother and Child Health, Bucharest, Romania
| | - M Luisa Mearin
- Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands
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46
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Niewiem M, Grzybowska-Chlebowczyk U. Intestinal Barrier Permeability in Allergic Diseases. Nutrients 2022; 14:nu14091893. [PMID: 35565858 PMCID: PMC9101724 DOI: 10.3390/nu14091893] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/25/2022] [Accepted: 04/28/2022] [Indexed: 02/01/2023] Open
Abstract
The role of intestinal permeability (IP) markers among children and adults with food allergies is not fully understood, and the identification of biological indicators/markers that predict growth retardation in children with allergic diseases and atopy has not been well explained. Studies have shown that patients with atopic diseases respond abnormally to food allergens. Accordingly, differences in the types of immune complexes formed in response to antigen challenges are significant, which seems to underlie the systemic signs of the food allergy. Increased intestinal permeability over the course of a food allergy allows allergens to penetrate through the intestinal barrier and stimulate the submucosal immune system. Additionally, the release of cytokines and inflammatory mediators enhances the degradation of the epithelial barrier and leads to an improper cycle, resulting in increased intestinal permeability. Several studies have also demonstrated increased permeability of the epithelial cells in those afflicted with atopic eczema and bronchial asthma. Ongoing research is aimed at finding various indicators to assess IP in patients with atopic diseases.
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Hieu DQ, Hang BTB, Lokesh J, Garigliany MM, Huong DTT, Yen DT, Liem PT, Tam BM, Hai DM, Son VN, Phuong NT, Farnir F, Kestemont P. Salinity significantly affects intestinal microbiota and gene expression in striped catfish juveniles. Appl Microbiol Biotechnol 2022; 106:3245-3264. [PMID: 35366085 DOI: 10.1007/s00253-022-11895-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/08/2022] [Accepted: 03/19/2022] [Indexed: 12/17/2022]
Abstract
In the present study, juvenile striped catfish (Pangasianodon hypophthalmus), a freshwater fish species, have been chronically exposed to a salinity gradient from freshwater to 20 psu (practical salinity unit) and were sampled at the beginning (D20) and the end (D34) of exposure. The results revealed that the intestinal microbial profile of striped catfish reared in freshwater conditions were dominated by the phyla Bacteroidetes, Firmicutes, Proteobacteria, and Verrucomicrobia. Alpha diversity measures (observed OTUs (operational taxonomic units), Shannon and Faith's PD (phylogenetic diversity)) showed a decreasing pattern as the salinities increased, except for the phylogenetic diversity at D34, which was showing an opposite trend. Furthermore, the beta diversity between groups was significantly different. Vibrio and Akkermansia genera were affected differentially with increasing salinity, the former being increased while the latter was decreased. The genus Sulfurospirillium was found predominantly in fish submitted to salinity treatments. Regarding the host response, the fish intestine likely contributed to osmoregulation by modifying the expression of osmoregulatory genes such as nka1a, nka1b, slc12a1, slc12a2, cftr, and aqp1, especially in fish exposed to 15 and 20 psu. The expression of heat shock proteins (hsp) hsp60, hsp70, and hsp90 was significantly increased in fish reared in 15 and 20 psu. On the other hand, the expression of pattern recognition receptors (PRRs) were inhibited in fish exposed to 20 psu at D20. In conclusion, the fish intestinal microbiota was significantly disrupted in salinities higher than 10 psu and these effects were proportional to the exposure time. In addition, the modifications of intestinal gene expression related to ion exchange and stressful responses may help the fish to adapt hyperosmotic environment. KEY POINTS: • It is the first study to provide detailed information on the gut microbiota of fish using the amplicon sequencing method. • Salinity environment significantly modified the intestinal microbiota of striped catfish. • Intestinal responses may help the fish adapt to hyperosmotic environment.
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Affiliation(s)
- Dang Quang Hieu
- Research Unit in Environmental and Evolutionary Biology, Institute of Life Earth & Environment (ILEE), University of Namur, Namur, Belgium.
| | - Bui Thi Bich Hang
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam
| | - Jep Lokesh
- Université de Pau Et Des Pays de L'Adour, Saint-Pee-sur-Nivelle, E2S UPPA, INRAE, NuMéA, France
| | - Mutien-Marie Garigliany
- Department of Pathology, Faculty of Veterinary Medicine, University of Liège, Liege, Belgium
| | - Do Thi Thanh Huong
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam
| | - Duong Thuy Yen
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam
| | - Pham Thanh Liem
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam
| | - Bui Minh Tam
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam
| | - Dao Minh Hai
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam.,Department of Animal Production, Faculty of Veterinary Medicine, University of Liège, Liege, Belgium
| | - Vo Nam Son
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam
| | - Nguyen Thanh Phuong
- College of Aquaculture and Fisheries, Can Tho University, Can Tho City, Vietnam
| | - Frédéric Farnir
- Department of Animal Production, Faculty of Veterinary Medicine, University of Liège, Liege, Belgium
| | - Patrick Kestemont
- Research Unit in Environmental and Evolutionary Biology, Institute of Life Earth & Environment (ILEE), University of Namur, Namur, Belgium.
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48
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Association between Gastrointestinal Diseases and Migraine. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19074018. [PMID: 35409704 PMCID: PMC8997650 DOI: 10.3390/ijerph19074018] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 02/06/2023]
Abstract
Migraine is a common disease worldwide, and recent studies showed that the incidence of migraine was increased in patients with gastrointestinal (GI) diseases. In addition, preclinical evidence suggested a bidirectional relationship between the GI nervous system and the central nervous system called the gut−brain axis. This study aimed to determine the association between several high-prevalence GI diseases and migraine. Patients diagnosed with migraine or GI diseases were classified as the patient group at least twice a year. We included peptic ulcer disease, dyspepsia, inflammatory bowel disease, irritable bowel syndrome, and gastroesophageal disease as GI diseases. A total of 781,115 patients from the HIRA dataset were included in the study. The prevalence of migraine was about 3.5 times higher in patients with one or more GI diseases after adjusting for age, gender, and insurance type (adjusted odds ratio (ORadj = 3.46, 95% CI: 3.30−3.63, p < 0.001). In addition, the prevalence of migraine was increased as the number of comorbid GI diseases increased. The prevalence of GI disease was also higher in patients with medication for migraine, both preventive and acute treatment, compared to patients with either acute preventive or acute treatment. There was a statistically significant association between the prevalence of GI diseases and migraine, and the higher the number of accompanying GI diseases, the higher the correlation was in patients using both preventive and acute treatment drugs for migraine.
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Stoeva MK, Garcia-So J, Justice N, Myers J, Tyagi S, Nemchek M, McMurdie PJ, Kolterman O, Eid J. Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut Microbes 2022; 13:1-28. [PMID: 33874858 PMCID: PMC8078720 DOI: 10.1080/19490976.2021.1907272] [Citation(s) in RCA: 229] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Clostridium butyricum is a butyrate-producing human gut symbiont that has been safely used as a probiotic for decades. C. butyricum strains have been investigated for potential protective or ameliorative effects in a wide range of human diseases, including gut-acquired infection, intestinal injury, irritable bowel syndrome, inflammatory bowel disease, neurodegenerative disease, metabolic disease, and colorectal cancer. In this review we summarize the studies on C. butyricum supplementation with special attention to proposed mechanisms for the associated health benefits and the supporting experimental evidence. These mechanisms center on molecular signals (especially butyrate) as well as immunological signals in the digestive system that cascade well beyond the gut to the liver, adipose tissue, brain, and more. The safety of probiotic C. butyricum strains appears well-established. We identify areas where additional human randomized controlled trials would provide valuable further data related to the strains' utility as an intervention.
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Affiliation(s)
- Magdalena K. Stoeva
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - Jeewon Garcia-So
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - Nicholas Justice
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - Julia Myers
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - Surabhi Tyagi
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - Madeleine Nemchek
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - Paul J. McMurdie
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - Orville Kolterman
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA
| | - John Eid
- R&D and Clinical departments, Pendulum Therapeutics, Inc, San Francisco, CA, USA,CONTACT John Eid Pendulum Therapeutics, Inc, San Francisco, California, USA
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Yong Y, Li J, Gong D, Yu T, Wu L, Hu C, Liu X, Yu Z, Ma X, Gooneratne R, El-Aty AMA, Chen J, Ju X. ERK1/2 mitogen-activated protein kinase mediates downregulation of intestinal tight junction proteins in heat stress-induced IBD model in pig. J Therm Biol 2021; 101:103103. [PMID: 34879918 DOI: 10.1016/j.jtherbio.2021.103103] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 08/25/2021] [Accepted: 09/15/2021] [Indexed: 01/13/2023]
Abstract
In many mammalian species, including pigs, heat stress (HS) detrimentally leads to epithelium damage and increases intestinal permeability. However, the underlying molecular mechanisms are not thoroughly investigated yet. This study aimed to examine the RIP1/RIP3-ERK1/2 signaling pathway that regulates the expression of tight junction proteins in HS-treated pigs. In in vitro cultured intestinal porcine epithelial cells (IPEC-J2), HS induced the expression of tight junction proteins, ZO-1, claudin-1, and claudin-4, that are regulated by the ERK1/2-MAPK signaling pathway. Further, high expression of HSP70 in IPEC-J2 cells induced a significant decrease in receptor-interacting protein 1/3 (RIP1/3), phosphorylated ERK, and tight junction protein claudin-1 (P < 0.05). Necrostatin-1 (A selective inhibitor of RIPK1) suppressed the upregulation of phosphorylated ERK1/2 induced by HS, indicating that the RIP1/RIP3 regulates ERK1/2 phosphorylation in IPEC-J2 under heat stress. In addition, HS significantly damaged the intestinal morphology characterized by reduction of villus length and crypt depth in in vivo porcine model. Moreover, the expression of tight junction, ZO-1, and claudin-4 were downregulated, whereas phosphorylated p38 and ERK1/2 were upregulated in the duodenum of heat-stressed pigs. Interestingly, a decrease in ZO-1 and claudin-1 was observed in the colon, where phosphorylated ERK1/2 was similar to that in the duodenum. Our results demonstrate that RIP1/RIP3-ERK1/2 signaling pathway regulates the expression of tight junction proteins in HS-pigs. This finding further advances the intestinal barrier function's underlying mechanisms associated with signaling regulation.
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Affiliation(s)
- Yanhong Yong
- Shenzhen Institute of Guangdong Ocean University, Shenzhen, 518018, China; Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Junyu Li
- Shenzhen Institute of Guangdong Ocean University, Shenzhen, 518018, China; Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Dongliang Gong
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Tianyue Yu
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Lianyun Wu
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Canying Hu
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Xiaoxi Liu
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Zhichao Yu
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Xingbin Ma
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China
| | - Ravi Gooneratne
- Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, 7647, New Zealand
| | - A M Abd El-Aty
- State Key Laboratory of Biobased Material and Green Papermaking, College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Science, Jinan, 250353, China; Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey
| | - Jinjun Chen
- Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China.
| | - Xianghong Ju
- Shenzhen Institute of Guangdong Ocean University, Shenzhen, 518018, China; Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, 524088, China.
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