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Uriot O, Deschamps C, Scanzi J, Brun M, Kerckhove N, Dualé C, Fournier E, Durif C, Denis S, Dapoigny M, Langella P, Alric M, Etienne-Mesmin L, Stéphanie BD. Gut microbial dysbiosis associated to diarrheic irritable bowel syndrome can be efficiently simulated in the Mucosal ARtificial COLon (M-ARCOL). Bioengineered 2025; 16:2458362. [PMID: 39902883 PMCID: PMC11796540 DOI: 10.1080/21655979.2025.2458362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 01/08/2025] [Accepted: 01/16/2025] [Indexed: 02/06/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, with diarrhea-predominant IBS (IBS-D) as the most frequent subtype. The implication of gut microbiota in the disease's etiology is not fully understood. In vitro gut systems can offer a great alternative to in vivo assays in preclinical studies, but no model reproducing IBS-related dysbiotic microbiota has been developed. Thanks to a large literature review, a new Mucosal ARtifical COLon (M-ARCOL) adapted to IBS-D physicochemical and nutritional conditions was set-up. To validate the model and further exploit its potential in a mechanistic study, in vitro fermentations were performed using bioreactors inoculated with stools from healthy individuals (n = 4) or IBS-D patients (n = 4), when the M-ARCOL was set-up under healthy or IBS-D conditions. Setting IBS-D parameters in M-ARCOL inoculated with IBS-D stools maintained the key microbial features associated to the disease in vivo, validating the new system. In particular, compared to the healthy control, the IBS-D model was characterized by a decreased bacterial diversity, together with a lower abundance of Rikenellaceae and Prevotellaceae, but a higher level of Proteobacteria and Akkermansiaceae. Of interest, applying IBS-D parameters to healthy stools was not sufficient to trigger IBS-D dysbiosis and applying healthy parameters to IBS-D stools was not enough to restore microbial balance. This validated IBS-D colonic model can be used as a robust in vitro platform for studies focusing on gut microbes in the absence of the host, as well as for testing food and microbiota-related interventions aimed at personalized restoration of gut microbiota eubiosis.
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Affiliation(s)
- Ophélie Uriot
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Charlotte Deschamps
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Julien Scanzi
- UMR INSERM 1107 NEURO-DOL, Université Clermont Auvergne, Clermont-Ferrand, Puy-de-Dôme,France
- Service de Gastroentérologie, Centre Hospitalo-Universitaire, Clermont-Ferrand, Puy-de-Dôme,France
- Service de Gastroentérologie, Centre Hospitalier de Thiers, Thiers, Puy-de-Dôme, France
| | - Morgane Brun
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Nicolas Kerckhove
- UMR INSERM 1107 NEURO-DOL, Université Clermont Auvergne, Clermont-Ferrand, Puy-de-Dôme,France
- Service de Pharmacologie médicale, Centre Hospitalo-Universitaire, Clermont-Ferrand, Puy-de-Dôme,France
| | - Christian Dualé
- CIC INSERM 1405, Centre Hospitalo-Universitaire, Clermont-Ferrand, Puy-de-Dôme,France
| | - Elora Fournier
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Claude Durif
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Sylvain Denis
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Michel Dapoigny
- UMR INSERM 1107 NEURO-DOL, Université Clermont Auvergne, Clermont-Ferrand, Puy-de-Dôme,France
- Service de Gastroentérologie, Centre Hospitalo-Universitaire, Clermont-Ferrand, Puy-de-Dôme,France
| | - Philippe Langella
- Micalis, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, Yvelines,France
| | - Monique Alric
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Lucie Etienne-Mesmin
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
| | - Blanquet-Diot Stéphanie
- UMR 454 MEDIS, Microbiologie Environnement Digestif et Santé, Université Clermont Auvergne – INRAE, Clermont-Ferrand, Puy-de-Dôme,France
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Barbara G, Aziz I, Ballou S, Chang L, Ford AC, Fukudo S, Nurko S, Olano C, Saps M, Sayuk G, Siah KTH, Van Oudenhove L, Simrén M. Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction. Nat Rev Gastroenterol Hepatol 2025; 22:228-251. [PMID: 39870943 DOI: 10.1038/s41575-024-01033-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/29/2025]
Abstract
In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood. This overlap has been shown to be of great relevance for DGBI. In addition, symptoms considered to be caused by a DGBI could have a detectable organic cause, and in patients with a diagnosed organic gastrointestinal disease, symptoms not clearly explained by the pathology defining this organic disease are common. Thus, the aims of this Rome Foundation Working Team Report were to review the literature on overlapping conditions among patients with paediatric and adult DGBI and, based on the available epidemiological and clinical evidence, make recommendations for the current diagnostic and therapeutic approach, and for future research. Specifically, we focused on other DGBI in the same or different gastrointestinal anatomical region(s), DGBI overlap with organic bowel diseases in remission, and DGBI overlap with non-gastrointestinal, non-structural conditions.
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Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Imran Aziz
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Sarah Ballou
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Shin Fukudo
- Department of Psychosomatic Medicine, Japanese Red Cross Ishinomaki Hospital, Research Center for Accelerator and Radioisotope Science, Tohoku University, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Samuel Nurko
- Center for Motility and Functional Gastrointestinal Disorders, Boston Children's Hospital, Boston, MA, USA
| | - Carolina Olano
- Gastroenterology Department. Universidad de la República, Montevideo, Uruguay
| | - Miguel Saps
- Division of Gastroenterology, Hepatology, and Nutrition, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Gregory Sayuk
- Gastroenterology Division, Washington University School of Medicine, St. Louis, MO, USA
- St. Louis Veterans Affairs Medical Center, St. Louis, MO, USA
| | - Kewin T H Siah
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore
| | - Lukas Van Oudenhove
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
- Leuven Brain Institute, KU Leuven, Leuven, Belgium
- Consultation-Liaison Psychiatry, University Psychiatric Centre KU Leuven, Leuven, Belgium
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Quan R, Decraecker L, Appeltans I, Cuende-Estévez M, Van Remoortel S, Aguilera-Lizarraga J, Wang Z, Hicks G, Wykosky J, McLean P, Denadai-Souza A, Hussein H, Boeckxstaens GE. Fecal Proteolytic Bacteria and Staphylococcal Superantigens Are Associated With Abdominal Pain Severity in Irritable Bowel Syndrome. Am J Gastroenterol 2025; 120:603-613. [PMID: 39166748 PMCID: PMC11864055 DOI: 10.14309/ajg.0000000000003042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 07/30/2024] [Indexed: 08/23/2024]
Abstract
INTRODUCTION Changes in the composition of the gut microbiota have been associated with the development of irritable bowel syndrome (IBS). However, to what extent specific bacterial species relate to clinical symptoms remains poorly characterized. We investigated the clinical relevance of bacterial species linked with increased proteolytic activity, histamine production, and superantigen (SAg) production in patients with IBS. METHODS Fecal (n = 309) and nasal (n = 214) samples were collected from patients with IBS and healthy volunteers (HV). Clinical symptoms and gut transit time were evaluated. Bacterial abundance in feces and nasal swabs as well as fecal trypsin-like activity were assessed. RESULTS The percentage of fecal samples containing Staphylococcus aureus was significantly higher in IBS compared with HV. Forty-nine percent of S. aureus -positive fecal samples from patients with IBS were also positive for SAgs, compared with 12% of HV. Patients with IBS and positive fecal SAg-producing S. aureus reported higher pain scores than those without S. aureus . Moreover, increased fecal proteolytic activity was associated with abdominal pain. Fecal abundance of Paraprevotella clara and Alistipes putredinis was significantly decreased in IBS, particularly in samples with higher proteolytic activity. Patients with lower Alistipes putredinis or Faecalibacterium prausnitzii abundance reported more severe abdominal pain. DISCUSSION In keeping with our preclinical findings, we show that increased presence of SAg-producing S. aureus in fecal samples of patients with IBS is associated with increased levels of abdominal pain. We also show that increased fecal proteolytic activity is associated with increased abdominal pain in patients with IBS.
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Affiliation(s)
- Runze Quan
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Lisse Decraecker
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Iris Appeltans
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - María Cuende-Estévez
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Samuel Van Remoortel
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Javier Aguilera-Lizarraga
- Laboratory of Sensory Neurophysiology and Pain, Department of Pharmacology, University of Cambridge, Cambridge, UK
| | - Zheng Wang
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | | | | | | | - Alexandre Denadai-Souza
- Laboratory of Mucosal Biology, Hepatology Research Unit, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Hind Hussein
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Guy E. Boeckxstaens
- Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
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Lei Y, Sun X, Ruan T, Lu W, Deng B, Zhou R, Mu D. Effects of Probiotics and Diet Management in Patients With Irritable Bowel Syndrome: A Systematic Review and Network Meta-analysis. Nutr Rev 2025:nuae217. [PMID: 39862384 DOI: 10.1093/nutrit/nuae217] [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] [Indexed: 01/27/2025] Open
Abstract
CONTEXT The efficacy of probiotics and diet management in irritable bowel syndrome (IBS) is controversial, and their relative effectiveness remains unclear. OBJECTIVE This study aimed to evaluate the effects of probiotics, diet management, and their combination on IBS. DATA SOURCES PubMed, Embase, Cochrane, and Web of Science were searched from inception to July 10, 2023, for relevant studies, including symptom relief, IBS-symptom severity score (-SSS), and IBS-quality of life measure (-QOL). DATA EXTRACTION Two investigators independently performed the data extraction and quality assessment. DATA ANALYSIS A network meta-analysis was performed using a frequentist approach and a random-effects model to estimate the relative risk (RR) and 95% CI. RESULTS Forty-four articles were eligible for this study. In relieving IBS symptoms, compared with a sham diet, a low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (low-FODMAP) diet (RR: 3.22; 95% CI: 1.70-6.26) and low-FODMAP diet combined with probiotics (RR: 17.79; 95% CI: 3.27-112.54) significantly relieved IBS symptoms. The control group showed significantly lower effectiveness than the probiotics group (RR: 0.47; 95% CI: 0.32-0.69). According to the surface under the cumulative rank curve (SUCRA), a low-FODMAP diet combined with probiotics (80.4%) had the best effect in relieving IBS symptoms, followed by a low-FODMAP diet (70.8%), probiotics (65.1%), and a gluten-free diet (54.3%). In reducing the total IBS-SSS, the low-FODMAP diet (90.5%) was the most effective, followed by the low-FODMAP diet combined with probiotics (76.6%), probiotics alone (62.3%), and gluten-free diet (28.3%). In reducing total IBS-QOL, probiotics (72.1%) ranked first, followed by gluten-free (57.0%) and low-FODMAP (56.9%) diets. Probiotics (34.9%) were associated with the lowest risk of adverse effects. CONCLUSION A low-FODMAP diet combined with probiotics is most effective in relieving IBS symptoms. A low-FODMAP diet is the most recommended diet for alleviating IBS severity, and probiotics were associated with improving the QOL of patients with IBS, with the fewest adverse events. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42024499113.
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Affiliation(s)
- Yupeng Lei
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xuemei Sun
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Tiechao Ruan
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Wenting Lu
- Integrated Care Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Bixin Deng
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Ruixi Zhou
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Dezhi Mu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Li X, Li X, Xiao H, Xu J, He J, Xiao C, Zhang B, Cao M, Hong W. Meta-analysis of gut microbiota alterations in patients with irritable bowel syndrome. Front Microbiol 2024; 15:1492349. [PMID: 39777150 PMCID: PMC11703917 DOI: 10.3389/fmicb.2024.1492349] [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: 09/06/2024] [Accepted: 12/03/2024] [Indexed: 01/11/2025] Open
Abstract
Introduction Irritable bowel syndrome (IBS) is a common chronic disorder of gastrointestinal function with a high prevalence worldwide. Due to its complex pathogenesis and heterogeneity, there is urrently no consensus in IBS research. Methods We collected and uniformly reanalyzed 1167 fecal 16S rRNA gene sequencing samples (623 from IBS patients and 544 from healthy subjects) from 9 studies. Using both a random effects (RE) model and a fixed effects (FE) model, we calculated the odds ratios for metrics including bacterial alpha diversity, beta diversity, common genera and pathways between the IBS and control groups. Results Significantly lower alpha-diversity indexes were observed in IBS patients by random effects model. Twenty-six bacterial genera and twelve predicted pathways were identified with significant odds ratios and classification potentials for IBS patients. Based on these feature, we used transfer learning to enhance the predictive capabilities of our model, which improved model performance by approximately 10%. Moreover, through correlation network analysis, we found that Ruminococcaceae and Christensenellaceae were negatively correlated with vitamin B6 metabolism, which was decreased in the patients with IBS. Ruminococcaceae was also negatively correlated with tyrosine metabolism, which was decreased in the patients with IBS. Discussion This study revealed the dysbiosis of fecal bacterial diversity, composition, and predicted pathways of patients with IBS by meta-analysis and identified universal biomarkers for IBS prediction and therapeutic targets.
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Affiliation(s)
- Xiaxi Li
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Xiaoling Li
- College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Haowei Xiao
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Jiaying Xu
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Jianquan He
- Department of Rehabilitation, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, Xiamen, China
| | - Chuanxing Xiao
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Bangzhou Zhang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Man Cao
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Wenxin Hong
- Department of Rehabilitation, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, Xiamen, China
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Aluthge N, Adams S, Davila CA, Gocchi Carrasco NR, Chiou KS, Abadie R, Bennett SJ, Dombrowski K, Major AM, Valentín-Acevedo A, West JT, Wood C, Fernando SC. Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico. Front Microbiol 2024; 15:1470037. [PMID: 39697649 PMCID: PMC11652967 DOI: 10.3389/fmicb.2024.1470037] [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: 07/24/2024] [Accepted: 10/23/2024] [Indexed: 12/20/2024] Open
Abstract
Introduction The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use. Methods Using amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use. Results and discussion Our findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.
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Affiliation(s)
- Nirosh Aluthge
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, United States
| | - Seidu Adams
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, United States
| | - Carmen A. Davila
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, United States
| | | | - Kathy S. Chiou
- Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, United States
| | - Roberto Abadie
- Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, United States
| | - Sydney J. Bennett
- Department of Biological Science, University of Nebraska-Lincoln, Lincoln, NE, United States
| | | | - Angel M. Major
- Department of Microbiology and Immunology, Universidad Central del Caribe, Bayamon, Puerto Rico
| | - Aníbal Valentín-Acevedo
- Department of Microbiology and Immunology, Universidad Central del Caribe, Bayamon, Puerto Rico
| | - John T. West
- Department of Interdisciplinary Oncology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, United States
| | - Charles Wood
- Department of Interdisciplinary Oncology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, United States
| | - Samodha C. Fernando
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, United States
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Aggeletopoulou I, Triantos C. Microbiome Shifts and Their Impact on Gut Physiology in Irritable Bowel Syndrome. Int J Mol Sci 2024; 25:12395. [PMID: 39596460 PMCID: PMC11594715 DOI: 10.3390/ijms252212395] [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: 11/01/2024] [Revised: 11/17/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders characterized by recurrent abdominal pain and altered bowel habits. The exact pathophysiological mechanisms for IBS development are not completely understood. Several factors, including genetic predisposition, environmental and psychological influences, low-grade inflammation, alterations in gastrointestinal motility, and dietary habits, have been implicated in the pathophysiology of the disorder. Additionally, emerging evidence highlights the role of gut microbiota in the pathophysiology of IBS. This review aims to thoroughly investigate how alterations in the gut microbiota impact physiological functions such as the brain-gut axis, immune system activation, mucosal inflammation, gut permeability, and intestinal motility. Our research focuses on the dynamic "microbiome shifts", emphasizing the enrichment or depletion of specific bacterial taxa in IBS and their profound impact on disease progression and pathology. The data indicated that specific bacterial populations are implicated in IBS, including reductions in beneficial species such as Lactobacillus and Bifidobacterium, along with increases in potentially harmful bacteria like Firmicutes and Proteobacteria. Emphasis is placed on the imperative need for further research to delineate the role of specific microbiome alterations and their potential as therapeutic targets, providing new insights into personalized treatments for IBS.
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Affiliation(s)
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece;
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Taghaddos D, Saqib Z, Bai X, Bercik P, Collins SM. Post-infectious ibs following Clostridioides difficile infection; role of microbiota and implications for treatment. Dig Liver Dis 2024; 56:1805-1809. [PMID: 38653643 DOI: 10.1016/j.dld.2024.03.008] [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: 01/16/2024] [Revised: 02/21/2024] [Accepted: 03/13/2024] [Indexed: 04/25/2024]
Abstract
Up to 25% of patients recovering from antibiotic-treated Clostridioides difficile infection (CDI) develop functional symptoms reminiscent of Post-Infectious Irritable Bowel Syndrome (PI-IBS). For patients with persistent symptoms following infection, a clinical dilemma arises as to whether to provide additional antibiotic treatment or to adopt a conservative symptom-based approach. Here, we review the literature on CDI-related PI-IBS and compare the findings with PI-IBS. We review proposed mechanisms, including the role of C. difficile toxins and the microbiota, and discuss implications for therapy. We suggest that gut dysfunction post-CDI may be initiated by toxin-induced damage to enteroglial cells and that a dysbiotic gut microbitota maintains the clinical phenotype over time, prompting consideration of microbiota-directed therapies. While Fecal Microbial Transplant (FMT) is currently reserved for recurrent CDI (rCDI), we propose that microbiota-directed therapies may have a role in primary CDI in order to avoid or mitigate futher antibiotic treatment that further disrupts the microbiota and thus prevent PI-IBS. We discuss novel microbial transfer therapies and as they emerge, we recommend clinical trials to determine whether microbial transfer therapy of the primary infection prevents both rCDI and CDI-related PI- IBS.
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Affiliation(s)
- Dana Taghaddos
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Zarwa Saqib
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Xiaopeng Bai
- Division of Gastroenterology, Kyushu University, Japan
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Stephen M Collins
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
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9
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Cheng X, Ren C, Mei X, Jiang Y, Zhou Y. Gut microbiota and irritable bowel syndrome: status and prospect. Front Med (Lausanne) 2024; 11:1429133. [PMID: 39484201 PMCID: PMC11524842 DOI: 10.3389/fmed.2024.1429133] [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: 05/07/2024] [Accepted: 10/07/2024] [Indexed: 11/03/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a very common gastrointestinal disease that, although not as aggressive as tumors, affects patients' quality of life in different ways. The cause of IBS is still unclear, but more and more studies have shown that the characteristics of the gut microbiota, such as diversity, abundance, and composition, are altered in patients with IBS, compared to the healthy population, which confirms that the gut microbiota plays a crucial role in the development of IBS. This paper aims to identify the commonalities by reviewing a large body of literature. Changes in the characteristics of gut microbiota in patients with different types of IBS are discussed, relevant mechanisms are described, and the treatment modalities of gut microbiota in IBS are summarized. Although there are more clinical trials that have made good progress, more standardized, more generalized, larger-scale, multi-omics clinical studies are what is missing. Overall, gut microbiota plays a crucial role in the development of IBS, and there is even more potential for treating IBS by modulating gut microbiota.
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Affiliation(s)
- Xinyu Cheng
- Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, China
| | - Cheng Ren
- Department of Cardiology, The First people’s Hospital of Zhangjiagang, Affiliated Hospital of Soochow University, Medical Center of Soochow University, Zhangjiagang, Jiangsu, China
| | - Xiaofei Mei
- Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, China
| | - Yufeng Jiang
- Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, China
- Institute for Hypertension, Soochow University, Suzhou, China
| | - Yafeng Zhou
- Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, China
- Institute for Hypertension, Soochow University, Suzhou, China
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10
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Jiang S, Pei L, Chen L, Sun J, Song Y. Mechanisms of Electroacupuncture in Alleviating Visceral Hypersensitivity in Post-Infectious Irritable Bowel Syndrome Mice: The Role of GDNF Signaling Pathway and Gut Microbiota. Microb Physiol 2024; 34:255-263. [PMID: 39396501 DOI: 10.1159/000541888] [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: 11/09/2023] [Accepted: 10/07/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Post-infectious irritable bowel syndrome (PI-IBS) is a functional bowel disease that develops following an acute gastrointestinal infection. Electroacupuncture (EA) can regulate the gut microbiota and alleviate visceral hypersensitivity. Glial cell-derived neurotrophic factor (GDNF) is a potential factor in visceral hypersensitivity reactions. The aim of this study was to explore whether EA could alleviate visceral hypersensitivity in PI-IBS by regulating gut microbiota through GDNF signaling. METHODS 2,4,6-trinitrobenzene sulfonic acid was used to induce visceral hypersensitivity in PI-IBS mice. Intestinal visceral sensitivity was assessed by using the abdominal withdrawal reflex (colorectal distention). 16S ribosomal RNA sequencing profiles the gut microbiome community. RESULTS GDNF can exacerbate the imbalances of the gut microbiota and increase visceral hypersensitivity compared with the model group. Whereas EA treatment increases the richness and diversity of the gut microbiota, decreases differences among species and alleviates visceral sensitivity. CONCLUSION EA can alleviate visceral hypersensitivity in PI-IBS by regulating the gut microbiota via GDNF signaling, providing new insights for mechanistic research on EA in PI-IBS treatment.
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Affiliation(s)
- Shiyuan Jiang
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China,
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China,
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China,
| | - Lixia Pei
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lu Chen
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianhua Sun
- Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yafang Song
- Acupuncture and Massage College, Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, China
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11
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Teige ES, Hillestad EMR, Steinsvik EK, Brønstad I, Lundervold A, Lundervold AJ, Valeur J, Hausken T, Berentsen B, Lied GA. Fecal bacteria and short-chain fatty acids in irritable bowel syndrome: Relations to subtype. Neurogastroenterol Motil 2024; 36:e14854. [PMID: 38946176 DOI: 10.1111/nmo.14854] [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: 11/01/2023] [Revised: 05/16/2024] [Accepted: 06/15/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND The relationship between gut microbiota and irritable bowel syndrome (IBS) subtype is unclear. We aimed to explore whether differences in fecal bacteria composition and short-chain fatty acid (SCFA) levels were associated with subtypes and symptoms of IBS. METHODS All participants delivered fecal samples and self-reports on IBS Symptom Severity Score (IBS-SSS), Bristol Stool Scale (BSS), and Gastrointestinal Symptom Rating Scale (GSRS). Fecal bacteria composition was assessed by the GA-map® Dysbiosis Test based on 16S rRNA sequences of bacterial species/groups. SCFAs were analyzed by vacuum distillation followed by gas chromatography. KEY RESULTS Sixty patients with IBS were included (mean age 38 years, 46 [77%] females): Twenty-one patients were classified as IBS-D (diarrhea), 31 IBS-M (mixed diarrhea and constipation), and eight IBS-C (constipation). Forty-two healthy controls (HCs) (mean age 35 years, 27 [64%] females) were included. Patients had a significantly higher relative frequency of dysbiosis, lower levels of Actinobacteria, and higher levels of Bacilli than HCs. Eight bacterial markers were significantly different across IBS subgroups and HCs, and 13 bacterial markers were weakly correlated with IBS symptoms. Clostridia and Veillonella spp. had a weak negative correlation with constipation scores (GSRS) and a weak positive correlation with loose stools (BSS). Diarrhea scores (GSRS) and looser stool (BSS) were weakly correlated with levels of total SCFAs, acetic and butyric acid. Levels of total SCFAs and acetic acid were weakly correlated with symptom severity (IBS-SSS). CONCLUSIONS & INFERENCES Patients with IBS had a different fecal bacteria composition compared to HCs, and alterations of SCFAs may contribute to the subtype.
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Affiliation(s)
- Erica Sande Teige
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Eline Margrete Randulff Hillestad
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Elisabeth Kjelsvik Steinsvik
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Ingeborg Brønstad
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Arvid Lundervold
- Mohn Medical Imaging and Visualization Centre, Haukeland University Hospital, Bergen, Norway
- Department of Biomedicine, University of Bergen, Bergen, Norway
| | - Astri J Lundervold
- Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway
| | - Jørgen Valeur
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital Oslo, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Trygve Hausken
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Birgitte Berentsen
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Gülen Arslan Lied
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway
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12
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Hartikainen AK, Jalanka J, Lahtinen P, Ponsero AJ, Mertsalmi T, Finnegan L, Crispie F, Cotter PD, Arkkila P, Satokari R. Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients. NPJ Biofilms Microbiomes 2024; 10:73. [PMID: 39191760 PMCID: PMC11349920 DOI: 10.1038/s41522-024-00549-x] [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: 03/25/2024] [Accepted: 08/20/2024] [Indexed: 08/29/2024] Open
Abstract
Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.
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Affiliation(s)
- Anna K Hartikainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
| | - Jonna Jalanka
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Perttu Lahtinen
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Gastroenterology, Päijät-Häme Central Hospital, Lahti, Finland
| | - Alise J Ponsero
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- BIO5 Institute and Department of Biosystems Engineering, University of Arizona, Tucson, AZ, USA
| | - Tuomas Mertsalmi
- Department of Neurology, Helsinki University Hospital HUS, Helsinki, Finland
- Department of Clinical Neurosciences, University of Helsinki, HUS, PO Box 800, FI-00029, Helsinki, Finland
| | - Laura Finnegan
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
- APC Microbiome, Ireland, Cork, Ireland
| | - Fiona Crispie
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
- APC Microbiome, Ireland, Cork, Ireland
| | - Paul D Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
- APC Microbiome, Ireland, Cork, Ireland
| | - Perttu Arkkila
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | - Reetta Satokari
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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13
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Gryaznova M, Smirnova Y, Burakova I, Morozova P, Lagutina S, Chizhkov P, Korneeva O, Syromyatnikov M. Fecal Microbiota Characteristics in Constipation-Predominant and Mixed-Type Irritable Bowel Syndrome. Microorganisms 2024; 12:1414. [PMID: 39065182 PMCID: PMC11278693 DOI: 10.3390/microorganisms12071414] [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: 06/20/2024] [Revised: 07/09/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common condition that affects the lifestyle of patients. It is associated with significant changes in the composition of the gut microbiome, but the underlying microbial mechanisms remain to be fully understood. We study the fecal microbiome of patients with constipation-predominant IBS (IBS-C) and mixed-type IBS (IBS-M). METHODS We sequenced the V3 region of the 16S rRNA on the Ion Torrent PGM sequencing platform to study the microbiome. RESULTS In the patients with IBS-C and IBS-M, an increase in alpha diversity was found, compared to the healthy group, and differences in beta diversity were also noted. At the phylum level, both IBS subtypes showed an increase in the Firmicutes/Bacteroidetes ratio, as well as an increase in the abundance of Actinobacteria and Verrucomicrobiota. Changes in some types of bacteria were characteristic of only one of the IBS subtypes, while no statistically significant differences in the composition of the microbiome were detected between IBS-C and IBS-M. CONCLUSIONS This study was the first to demonstrate the association of Turicibacter sanguinis, Mitsuokella jalaludinii, Erysipelotrichaceae UCG-003, Senegalimassilia anaerobia, Corynebacterium jeikeium, Bacteroides faecichinchillae, Leuconostoc carnosum, and Parabacteroides merdae with IBS subtypes.
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Affiliation(s)
- Mariya Gryaznova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Yuliya Smirnova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Inna Burakova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Polina Morozova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia;
| | - Svetlana Lagutina
- Department of Polyclinic Therapy, Voronezh State Medical University Named after N.N. Burdenko, 394036 Voronezh, Russia;
| | - Pavel Chizhkov
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia;
| | - Olga Korneeva
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
| | - Mikhail Syromyatnikov
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia; (M.G.); (Y.S.); (I.B.); (P.M.); (O.K.)
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia;
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14
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JohnBritto JS, Di Ciaula A, Noto A, Cassano V, Sciacqua A, Khalil M, Portincasa P, Bonfrate L. Gender-specific insights into the irritable bowel syndrome pathophysiology. Focus on gut dysbiosis and permeability. Eur J Intern Med 2024; 125:10-18. [PMID: 38467533 DOI: 10.1016/j.ejim.2024.03.011] [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: 02/08/2024] [Accepted: 03/05/2024] [Indexed: 03/13/2024]
Abstract
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder involving the brain-gut interaction. IBS is characterized by persistent abdominal pain and changes in bowel habits. IBS exerts significant impacts on quality of life and imposes huge economic costs. Global epidemiological data reveal variations in IBS prevalence, both globally and between genders, necessitating comprehensive studies to uncover potential societal and cultural influences. While the exact pathophysiology of IBS remains incompletely understood, the mechanism involves a dysregulation of the brain-gut axis, leading to disturbed intestinal motility, local inflammation, altered intestinal permeability, visceral sensitivity, and gut microbiota composition. We reviewed several gender-related pathophysiological aspects of IBS pathophysiology, by focusing on gut dysbiosis and intestinal permeability. This perspective paves the way to personalized and multidimensional clinical management of individuals with IBS.
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Affiliation(s)
- Jerlin Stephy JohnBritto
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Antonino Noto
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Velia Cassano
- Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Mohamad Khalil
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy.
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
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15
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Thomas-Dupont P, Izaguirre-Hernández IY, Roesch-Dietlen F, Grube-Pagola P, Reyes-Huerta J, Remes-Troche JM. Prevalence of Anti- Saccharomyces Cerevisiae Antibodies (ASCA) in Patients With Irritable Bowel Syndrome (IBS). A Case-control Study. J Clin Gastroenterol 2024; 58:483-486. [PMID: 37540063 DOI: 10.1097/mcg.0000000000001896] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 06/22/2023] [Indexed: 08/05/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects patients' quality. Recent research has shown variations in the mycobiome of individuals with IBS, particularly involving Saccharomyces cerevisiae , and its association with dysbiosis and visceral hypersensitivity. However, the role of Anti-Saccharomyces cerevisiae antibodies (ASCA) in IBS remains unclear, despite their significance as markers of disease severity in inflammatory bowel disease. OBJECTIVE This study aimed to investigate the role of ASCA in Mexican IBS patients compared with healthy controls (HCs) and determine whether these antibodies could help differentiate between IBS patients and healthy individuals. METHODS Serum samples from 400 IBS patients and 400 HC were analyzed. ASCA IgG levels were measured using enzyme-linked immunosorbent assay (ELISA). The IBS patients were further categorized into subtypes: constipation predominant (IBS-C), diarrhea predominant (IBS-D), and mixed (IBS-M). RESULTS Among the participants, 66 IBS patients (16.5%) and 63 HC (15.75%) tested positive for ASCA IgG. No significant difference was observed in ASCA IgG levels between the 2 groups ( P value: 0.8451). The prevalence of ASCA IgG positivity was 14.5% in IBS-C, 17.8% in IBS-D, and 15.9% in IBS-M. CONCLUSION Surprisingly, a high prevalence of ASCA IgG was found in the HC group in Mexico. Furthermore, there was no significant difference in ASCA IgG levels between IBS patients and controls. These findings suggest that ASCA is not useful as a discriminatory biomarker for distinguishing IBS patients from healthy individuals and cannot serve as a surrogate marker for visceral hypersensitivity.
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Affiliation(s)
| | | | - Federico Roesch-Dietlen
- Digestive Physiology and Motility Lab. Medical Biological Research Institute. University of Veracruz
| | - Peter Grube-Pagola
- Digestive Physiology and Motility Lab. Medical Biological Research Institute. University of Veracruz
| | - Job Reyes-Huerta
- Digestive Physiology and Motility Lab. Medical Biological Research Institute. University of Veracruz
| | - José María Remes-Troche
- Digestive Physiology and Motility Lab. Medical Biological Research Institute. University of Veracruz
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16
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Teige ES, Sortvik U, Lied GA. A Systematic Review: Fecal Bacterial Profile in Patients with Irritable Bowel Syndrome Analyzed with the GA-Map Dysbiosis Test Based on the 16S rRNA Gene of Bacterial Species or Groups. Clin Exp Gastroenterol 2024; 17:109-120. [PMID: 38646157 PMCID: PMC11032674 DOI: 10.2147/ceg.s451675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 03/20/2024] [Indexed: 04/23/2024] Open
Abstract
Purpose The diagnosis of irritable bowel syndrome (IBS) is based on symptom-based criteria due to lack of reliable disease-specific biomarkers. Gut microbiota is perturbed in IBS and when comparing different methods used to analyze gut microbiota, the results might be obscured. Therefore, in this systematic review we aimed to investigate the profile of fecal bacterial markers and dysbiosis index (DI) in patients with IBS and IBS subgroups compared to healthy controls (HCs) conducted by the same method (GA-map Dysbiosis Test based on16S rRNA sequencing). Material and Method We searched PubMed, EMBASE (Ovid) and Cochrane Library for case-control studies comparing fecal gut microbiota analyzed with the GA-map® Dysbiosis Test (Oslo, Norway) in patients with IBS and HCs. Our outcomes were the difference in fecal bacterial markers and DI in patients with IBS and IBS subgroups compared to HCs. Results The search identified 28 citations; five articles were included. Most studies evaluated fecal bacterial markers and DI in patients with diarrhea-predominant IBS (IBS-D). Results of fecal bacteria profile in IBS and IBS subgroups compared to HCs are inconsistent, however, two studies showed increased levels of Ruminococcus gnavus in IBS-D compared to HCs and results of DI indicated IBS and IBS subgroups (especially IBS-D) having higher DI compared to HCs. Conclusion This systematic review revealed inconsistent findings in respect to differences in bacterial markers between IBS and IBS subgroups with HCs in studies using the GA-map Dysbiosis Test based on 16S rRNA sequencing. However, the test is quite novel, and few studies have used the method so far. More research comparing fecal microbiota profile differences in IBS and IBS subgroups compared to HCs utilizing the same method of analysis is needed to give us further insight into the gut bacteria profile in IBS and the clinical consequences of intestinal dysbiosis.
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Affiliation(s)
- Erica Sande Teige
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Urd Sortvik
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Gülen Arslan Lied
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
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17
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Imbrea AM, Balta I, Dumitrescu G, McCleery D, Pet I, Iancu T, Stef L, Corcionivoschi N, Liliana PC. Exploring the Contribution of Campylobacter jejuni to Post-Infectious Irritable Bowel Syndrome: A Literature Review. APPLIED SCIENCES 2024; 14:3373. [DOI: 10.3390/app14083373] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
This comprehensive review investigates the specific impact of the foodborne pathogen Campylobacter jejuni (C. jejuni) on gastrointestinal health, focusing on its connection to post-infectious irritable bowel syndrome (PI-IBS). This review examines the pathogen’s pathophysiology, clinical implications and epidemiological trends using recent research and data to highlight its prevalence and association with PI-IBS. A detailed literature analysis synthesizes current research to illuminate Campylobacter’s long-lasting effects on gut microbiota and intestinal function. It provides a detailed analysis of the literature to shed light on C. jejuni’s long-term impact on gut microbiota and intestinal function. The findings suggest the need for multifaceted prevention and treatment approaches considering individual, microbial and epidemiological factors, thus contributing to a more nuanced understanding of PI-IBS following C. jejuni infection.
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Affiliation(s)
- Ana-Maria Imbrea
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Igori Balta
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Gabi Dumitrescu
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - David McCleery
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, UK
| | - Ioan Pet
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Tiberiu Iancu
- Faculty of Management and Rural Tourism, University of Life Sciences King Mihai I from Timisoara, 300645 Timisoara, Romania
| | - Lavinia Stef
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
| | - Nicolae Corcionivoschi
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, UK
- Academy of Romanian Scientists, Ilfov Street, No. 3, 050044 Bucharest, Romania
| | - Petculescu-Ciochina Liliana
- Faculty of Bioengineering of Animal Resources, University of Life Sciences King Michael I from Timisoara, 300645 Timisoara, Romania
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18
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Chen X, Zhu D, Ge R, Bao Z. Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 273:116140. [PMID: 38417315 DOI: 10.1016/j.ecoenv.2024.116140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 02/17/2024] [Accepted: 02/20/2024] [Indexed: 03/01/2024]
Abstract
Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1β, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.
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Affiliation(s)
- Xiuxiu Chen
- Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China; Research Center on Aging and Medicine, Fudan University, Shanghai, China
| | - Donghui Zhu
- The Department of Cardiovascular and Thoracic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Renshan Ge
- Department of Anaesthesiology of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
| | - Zhijun Bao
- Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China; Research Center on Aging and Medicine, Fudan University, Shanghai, China.
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19
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Aykur M, Malatyalı E, Demirel F, Cömert-Koçak B, Gentekaki E, Tsaousis AD, Dogruman-Al F. Blastocystis: A Mysterious Member of the Gut Microbiome. Microorganisms 2024; 12:461. [PMID: 38543512 PMCID: PMC10972062 DOI: 10.3390/microorganisms12030461] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/19/2024] [Accepted: 02/22/2024] [Indexed: 11/12/2024] Open
Abstract
Blastocystis is the most common gastrointestinal protist found in humans and animals. Although the clinical significance of Blastocystis remains unclear, the organism is increasingly being viewed as a commensal member of the gut microbiome. However, its impact on the microbiome is still being debated. It is unclear whether Blastocystis promotes a healthy gut and microbiome directly or whether it is more likely to colonize and persist in a healthy gut environment. In healthy people, Blastocystis is frequently associated with increased bacterial diversity and significant differences in the gut microbiome. Based on current knowledge, it is not possible to determine whether differences in the gut microbiome are the cause or result of Blastocystis colonization. Although it is possible that some aspects of this eukaryote's role in the intestinal microbiome remain unknown and that its effects vary, possibly due to subtype and intra-subtype variations and immune modulation, more research is needed to characterize these mechanisms in greater detail. This review covers recent findings on the effects of Blastocystis in the gut microbiome and immune modulation, its impact on the microbiome in autoimmune diseases, whether Blastocystis has a role like bacteria in the gut-brain axis, and its relationship with probiotics.
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Affiliation(s)
- Mehmet Aykur
- Department of Parasitology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat 60030, Türkiye
| | - Erdoğan Malatyalı
- Department of Parasitology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin 09010, Türkiye;
| | - Filiz Demirel
- Department of Medical Microbiology, Ankara City Hospital, Health Science University, Ankara 06500, Türkiye;
| | - Burçak Cömert-Koçak
- Department of Medical Microbiology, Karadeniz Ereğli State Hospital, Zonguldak 67300, Türkiye;
| | - Eleni Gentekaki
- Department of Veterinary Medicine, School of Veterinary Medicine, University of Nicosia, Nicosia 2414, Cyprus;
| | - Anastasios D. Tsaousis
- Laboratory of Molecular and Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury CT2 7NZ, UK;
| | - Funda Dogruman-Al
- Division of Medical Parasitology, Department of Medical Microbiology, Faculty of Medicine, Gazi University, Ankara 06560, Türkiye;
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20
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Alsaady IM. Cryptosporidium and irritable bowel syndrome. Trop Parasitol 2024; 14:8-15. [PMID: 38444793 PMCID: PMC10911187 DOI: 10.4103/tp.tp_10_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 10/16/2023] [Accepted: 10/22/2023] [Indexed: 03/07/2024] Open
Abstract
Cryptosporidium is an apicomplexan parasite that causes gastrointestinal disease in a wide variety of hosts and is associated with waterborne outbreaks. Nonetheless, the parasite is underdiagnosed. Cryptosporidium has been proposed as an etiological cause of irritable bowel syndrome (IBS) in several studies. However, the exact mechanism of pathogenesis is unknown, and no direct link has been discovered. This review will discuss several parasite-induced modifications, such as immunological, microbiome, and metabolite modifications, as well as their interactions. To summarize, Cryptosporidium causes low inflammation, dysbiosis, and unbalanced metabolism, which leads to a lack of homeostasis in the intestine in a comparable pattern to postinfectious IBS.
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Affiliation(s)
- Isra Mohammad Alsaady
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- King Fahad Medical Research Centre, Special Infectious Agents Unit, Jeddah, Saudi Arabia
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21
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Orgler E, Baumgartner M, Duller S, Kumptisch C, Hausmann B, Moser D, Khare V, Lang M, Köcher T, Frick A, Muttenthaler M, Makristathis A, Moissl-Eichinger C, Gasche C. Archaea influence composition of endoscopically visible ileocolonic biofilms. Gut Microbes 2024; 16:2359500. [PMID: 38825783 PMCID: PMC11152093 DOI: 10.1080/19490976.2024.2359500] [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: 10/06/2023] [Accepted: 05/21/2024] [Indexed: 06/04/2024] Open
Abstract
The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.
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Affiliation(s)
- Elisabeth Orgler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria
- Diagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
- Department of Medicine II, University Hospital, Munich, Germany
| | - Maximilian Baumgartner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria
| | - Stefanie Duller
- Diagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Christina Kumptisch
- Diagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Bela Hausmann
- Centre for Microbiology and Environmental Systems Science, Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria
- Division of Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Doris Moser
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria
| | - Vineeta Khare
- Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria
| | - Michaela Lang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria
- Centre for Microbiology and Environmental Systems Science, Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria
| | - Thomas Köcher
- Metabolomics Service and Research Facility, Vienna Biocenter Core Facilities, Vienna, Austria
| | - Adrian Frick
- Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria
| | - Markus Muttenthaler
- Faculty of Chemistry, Institute of Biological Chemistry, University of Vienna, Vienna, Austria
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
| | - Athanasios Makristathis
- Centre for Microbiology and Environmental Systems Science, Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria
- Division of Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Christine Moissl-Eichinger
- Diagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Christoph Gasche
- Division of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria
- Loha for Life, Center for Gastroenterology and Iron Deficiency, Vienna, Austria
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22
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Goodoory VC, Khasawneh M, Black CJ, Quigley EMM, Moayyedi P, Ford AC. Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis. Gastroenterology 2023; 165:1206-1218. [PMID: 37541528 DOI: 10.1053/j.gastro.2023.07.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 07/20/2023] [Accepted: 07/23/2023] [Indexed: 08/06/2023]
Abstract
BACKGROUND & AIMS Some probiotics may be beneficial in irritable bowel syndrome (IBS), but differences in species and strains used, as well as endpoints reported, have hampered attempts to make specific recommendations as to which should be preferred. We updated our previous meta-analysis examining this issue. METHODS MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to March 2023). Randomized controlled trials (RCTs) recruiting adults with IBS, comparing probiotics with placebo were eligible. Dichotomous symptom data were pooled to obtain a relative risk of global symptoms, abdominal pain, or abdominal bloating or distension persisting after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized mean difference with a 95% CI. Adverse events data were also pooled. RESULTS We identified 82 eligible trials, containing 10,332 patients. Only 24 RCTs were at low risk of bias across all domains. For global symptoms, there was moderate certainty in the evidence for a benefit of Escherichia strains, low certainty for Lactobacillus strains and Lactobacillus plantarum 299V, and very low certainty for combination probiotics, LacClean Gold S, Duolac 7s, and Bacillus strains. For abdominal pain, there was low certainty in the evidence for a benefit of Saccharomyces cerevisae I-3856 and Bifidobacterium strains, and very low certainty for combination probiotics, Lactobacillus, Saccharomyces, and Bacillus strains. For abdominal bloating or distension there was very low certainty in the evidence for a benefit of combination probiotics and Bacillus strains. The relative risk of experiencing any adverse event, in 55 trials, including more than 7000 patients, was not significantly higher with probiotics. CONCLUSIONS Some combinations of probiotics or strains may be beneficial in IBS. However, certainty in the evidence for efficacy by GRADE criteria was low to very low across almost all of our analyses.
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Affiliation(s)
- Vivek C Goodoory
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom
| | - Mais Khasawneh
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom
| | - Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas
| | - Paul Moayyedi
- Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.
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23
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Zheng H, Zhang C, Zhang J, Duan L. "Sentinel or accomplice": gut microbiota and microglia crosstalk in disorders of gut-brain interaction. Protein Cell 2023; 14:726-742. [PMID: 37074139 PMCID: PMC10599645 DOI: 10.1093/procel/pwad020] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 04/06/2023] [Indexed: 04/20/2023] Open
Abstract
Abnormal brain-gut interaction is considered the core pathological mechanism behind the disorders of gut-brain interaction (DGBI), in which the intestinal microbiota plays an important role. Microglia are the "sentinels" of the central nervous system (CNS), which participate in tissue damage caused by traumatic brain injury, resist central infection and participate in neurogenesis, and are involved in the occurrence of various neurological diseases. With in-depth research on DGBI, we could find an interaction between the intestinal microbiota and microglia and that they are jointly involved in the occurrence of DGBI, especially in individuals with comorbidities of mental disorders, such as irritable bowel syndrome (IBS). This bidirectional regulation of microbiota and microglia provides a new direction for the treatment of DGBI. In this review, we focus on the role and underlying mechanism of the interaction between gut microbiota and microglia in DGBI, especially IBS, and the corresponding clinical application prospects and highlight its potential to treat DGBI in individuals with psychiatric comorbidities.
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Affiliation(s)
- Haonan Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
- Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing 100191, China
| | - Cunzheng Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
- Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing 100191, China
| | - Jindong Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
- Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing 100191, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
- Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing 100191, China
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24
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Soussou S, Jablaoui A, Mariaule V, Kriaa A, Boudaya H, Wysocka M, Amouri A, Gargouri A, Lesner A, Maguin E, Rhimi M. Serine proteases and metalloproteases are highly increased in irritable bowel syndrome Tunisian patients. Sci Rep 2023; 13:17571. [PMID: 37845280 PMCID: PMC10579243 DOI: 10.1038/s41598-023-44454-3] [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: 07/24/2023] [Accepted: 10/09/2023] [Indexed: 10/18/2023] Open
Abstract
Serine proteases are involved in many biological processes and are associated with irritable bowel syndrome (IBS) pathology. An increase in serine protease activity has been widely reported in IBS patients. While most of the studies focused on host proteases, the contribution of microbial proteases are poorly studied. In the present study, we report the analysis of proteolytic activities in fecal samples from the first Tunisian cohort of IBS-M patients and healthy individuals. We demonstrated, for the first time, that metalloproteases activities were fourfold higher in fecal samples of IBS patients compared to controls. Of interest, the functional characterization of serine protease activities revealed a 50-fold increase in trypsin-like activities and a threefold in both elastase- and cathepsin G-like activities. Remarkably, we also showed a fourfold increase in proteinase 3-like activity in the case of IBS. This study also provides insight into the alteration of gut microbiota and its potential role in proteolytic modulation in IBS. Our results stressed the impact of the disequilibrium of serine proteases, metalloproteases and gut microbiota in IBS and the need of the further characterization of these targets to set out new therapeutic approaches.
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Affiliation(s)
- Souha Soussou
- Microbiota Interaction With Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, 78350, Jouy-en-Josas, France
- Laboratory of Molecular Biology of Eukaryotes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia
| | - Amin Jablaoui
- Microbiota Interaction With Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, 78350, Jouy-en-Josas, France
| | - Vincent Mariaule
- Microbiota Interaction With Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, 78350, Jouy-en-Josas, France
| | - Aicha Kriaa
- Microbiota Interaction With Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, 78350, Jouy-en-Josas, France
| | - Houda Boudaya
- Laboratory of Molecular Biology of Eukaryotes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia
| | | | - Ali Amouri
- Department of Gastroenterology, Hedi Chaker University Hospital, Sfax, Tunisia
| | - Ali Gargouri
- Laboratory of Molecular Biology of Eukaryotes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia
| | - Adam Lesner
- Faculty of Chemistry, University of Gdansk, Gdańsk, Poland
| | - Emmanuelle Maguin
- Microbiota Interaction With Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, 78350, Jouy-en-Josas, France
| | - Moez Rhimi
- Microbiota Interaction With Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, 78350, Jouy-en-Josas, France.
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25
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Garcia-Mazcorro JF, Amieva-Balmori M, Triana-Romero A, Wilson B, Smith L, Reyes-Huerta J, Rossi M, Whelan K, Remes-Troche JM. Fecal Microbial Composition and Predicted Functional Profile in Irritable Bowel Syndrome Differ between Subtypes and Geographical Locations. Microorganisms 2023; 11:2493. [PMID: 37894151 PMCID: PMC10608977 DOI: 10.3390/microorganisms11102493] [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: 08/16/2023] [Revised: 09/25/2023] [Accepted: 09/27/2023] [Indexed: 10/29/2023] Open
Abstract
Increasing evidence suggests a microbial pathogenesis in irritable bowel syndrome (IBS) but the relationship remains elusive. Fecal DNA samples from 120 patients with IBS, 82 Mexican (IBS-C: n = 33, IBS-D: n = 24, IBS-M: n = 25) and 38 British (IBS-C: n = 6, IBS-D: n = 27, IBS-M: n = 5), were available for analysis using 16S rRNA gene sequencing. Firmicutes (mean: 82.1%), Actinobacteria (10.2%), and Bacteroidetes (4.4%) were the most abundant taxa. The analysis of all samples (n = 120), and females (n = 94) only, showed no significant differences in bacterial microbiota, but the analysis of Mexican patients (n = 82) showed several differences in key taxa (e.g., Faecalibacterium) among the different IBS subtypes. In IBS-D there were significantly higher Bacteroidetes in British patients (n = 27) than in Mexican patients (n = 24), suggesting unique fecal microbiota signatures within the same IBS subtype. These differences in IBS-D were also observed at lower phylogenetic levels (e.g., higher Enterobacteriaceae and Streptococcus in Mexican patients) and were accompanied by differences in several alpha diversity metrics. Beta diversity was not different among IBS subtypes when using all samples, but the analysis of IBS-D patients revealed consistent differences between Mexican and British patients. This study suggests that fecal microbiota is different between IBS subtypes and also within each subtype depending on geographical location.
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Affiliation(s)
| | - Mercedes Amieva-Balmori
- Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
| | - Arturo Triana-Romero
- Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
| | - Bridgette Wilson
- Department of Nutritional Sciences, King’s College London, London WC2R 2LS, UK
| | - Leanne Smith
- Department of Nutritional Sciences, King’s College London, London WC2R 2LS, UK
| | - Job Reyes-Huerta
- Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
| | - Megan Rossi
- Department of Nutritional Sciences, King’s College London, London WC2R 2LS, UK
| | - Kevin Whelan
- Department of Nutritional Sciences, King’s College London, London WC2R 2LS, UK
| | - Jose M. Remes-Troche
- Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
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26
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Mizoguchi A, Higashiyama M, Wada A, Nishimura H, Tomioka A, Ito S, Tanemoto R, Nishii S, Inaba K, Sugihara N, Hanawa Y, Horiuchi K, Okada Y, Kurihara C, Akita Y, Narimatu K, Komoto S, Tomita K, Kawauchi S, Sato S, Hokari R. Visceral hypersensitivity induced by mild traumatic brain injury via the corticotropin-releasing hormone receptor: An animal model. Neurogastroenterol Motil 2023; 35:e14634. [PMID: 37357384 DOI: 10.1111/nmo.14634] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 03/30/2023] [Accepted: 06/12/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Mild blast-induced traumatic brain injury (bTBI) induces various gut symptoms resembling human irritable bowel syndrome (IBS) as one of mental and behavioral disorders. However, the underlying mechanisms remain unclear. We investigated whether the extremely localized brain impact extracranially induced by laser-induced shock wave (LISW) evoked IBS-like phenomenon including visceral hypersensitivity and intestinal hyperpermeability in rats. METHODS The rats were subjected to LISW on the scalp to shock the entire brain. Visceral hypersensitivity was evaluated by the threshold pressure of abdominal withdrawal reflex (AWR) using a colorectal distension test. Permeability was evaluated by the concentration of penetrating FITC-dextran from intestine and the mRNA expression levels of tight junction family proteins. Involvement of corticotropin-releasing factor receptor (CRFR) 1 and 2 was examined by evaluating mRNA expression and modulating CRFR function with agonist, recombinant CRF (10 μg/kg), and antagonist, astressin (33 μg/kg). High-throughput sequencing of the gut microbiota was performed by MiSeqIII instrument and QIIME tool. KEY RESULTS The thresholds of the AWR were significantly lowered after LISW. Permeability was increased in small intestine by LISW along with decreased expression of tight junction ZO-1. LISW significantly increased CRFR1 expression and decreased CRFR2 expression. Visceral hypersensitivity was significantly aggravated by CRFR agonist and suppressed by CRFR antagonist. The α- and β-diversity of the fecal microbiota was altered after LISW. CONCLUSIONS AND INFERENCES LISW provoked visceral hypersensitivity, small intestinal hyperpermeability, altered expression of CRFRs and changes in the microbiota, suggesting that genuine bTBI caused by LISW can induce a pathophysiology comparable to that of human IBS.
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Affiliation(s)
- Akinori Mizoguchi
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Masaaki Higashiyama
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Akinori Wada
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Hiroyuki Nishimura
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Akira Tomioka
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Suguru Ito
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Rina Tanemoto
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Shin Nishii
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Kenichi Inaba
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Nao Sugihara
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Yoshinori Hanawa
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Kazuki Horiuchi
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Yoshikiyo Okada
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Chie Kurihara
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Yoshihiro Akita
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Kazuyuki Narimatu
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Shunsuke Komoto
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Kengo Tomita
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
| | - Satoko Kawauchi
- Division of Bioinformation and Therapeutic Systems, National Defense Medical College Research Institute, Saitama, Japan
| | - Shunichi Sato
- Division of Bioinformation and Therapeutic Systems, National Defense Medical College Research Institute, Saitama, Japan
| | - Ryota Hokari
- Department of Internal Medicine, National Defense Medical College, Saitama, Japan
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Zheng C, Zhong Y, Zhang W, Wang Z, Xiao H, Zhang W, Xie J, Peng X, Luo J, Xu W. Chlorogenic Acid Ameliorates Post-Infectious Irritable Bowel Syndrome by Regulating Extracellular Vesicles of Gut Microbes. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2302798. [PMID: 37616338 PMCID: PMC10558682 DOI: 10.1002/advs.202302798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 08/01/2023] [Indexed: 08/26/2023]
Abstract
Post-infectious irritable bowel syndrome (PI-IBS) occurs after acute infectious diarrhea, and dysbiosis can be involved in its pathogenesis. Here, the role of chlorogenic acid (CGA) is investigated, a natural compound with several pharmacological properties, in alleviating PI-IBS in rats. It is elucidated that the gut microbiota plays a key role in PI-IBS pathogenesis and that rectal administration of CGA alleviated PI-IBS by modulating the gut microbiota and its metabolites. CGA supplementation significantly increased fecal Bacteroides acidifaciens abundance and glycine levels. Glycine structurally altered B. acidifaciens extracellular vesicles (EVs) and enriched functional proteins in the EVs; glycine-induced EVs alleviated PI-IBS by reducing inflammation and hypersensitivity of the intestinal viscera and maintaining mucosal barrier function. Moreover, B. acidifaciens EVs are enriched in the brain tissue. Thus, CGA mediates the mitigation of PI-IBS through the gut microbiota and its metabolites. This study proposes a novel mechanism of signal exchange between the gut microenvironment and the host.
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Affiliation(s)
- Cihua Zheng
- Department of General SurgeryThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
- Department of Rehabilitation MedicineThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Yuchun Zhong
- Department of General SurgeryThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Wenming Zhang
- Department of General SurgeryThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Zhuoya Wang
- Department of Rehabilitation MedicineThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Haili Xiao
- Department of Rehabilitation MedicineThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Wenjun Zhang
- Department of Rehabilitation MedicineThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Jian Xie
- Department of Rehabilitation MedicineThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Xiaogang Peng
- Jiangxi Province Key Laboratory of Molecular MedicineThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi330006P. R. China
| | - Jun Luo
- Department of Rehabilitation MedicineThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
| | - Wei Xu
- Department of General SurgeryThe Second Affiliated Hospital of Nanchang University1 Minde RoadNanchangJiangxi330006P. R. China
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Napolitano M, Fasulo E, Ungaro F, Massimino L, Sinagra E, Danese S, Mandarino FV. Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications. Microorganisms 2023; 11:2369. [PMID: 37894027 PMCID: PMC10609453 DOI: 10.3390/microorganisms11102369] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 10/29/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.
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Affiliation(s)
- Maria Napolitano
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Ernesto Fasulo
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Federica Ungaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Luca Massimino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy;
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Francesco Vito Mandarino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (E.F.); (F.U.); (L.M.); (S.D.); (F.V.M.)
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Lin W, Wu D, Zeng Y, Liu Y, Yu D, Wei J, Cai Y, Lin Y, Wu B, Huang H. Characteristics of gut microbiota in male periadolescent rats with irritable bowel syndrome. Heliyon 2023; 9:e18995. [PMID: 37609414 PMCID: PMC10440515 DOI: 10.1016/j.heliyon.2023.e18995] [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: 05/24/2023] [Revised: 07/26/2023] [Accepted: 08/04/2023] [Indexed: 08/24/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder, however, its effect on gut microbiota during the periadolescent period remains unclear. In this study, our objective was to investigate the characteristics of gut microbiota in male periadolescent rats with IBS induced by neonatal maternal separation (NMS). We evaluated visceral sensitivity by electromyography (EMG), analyzed gut microbiota composition using 16S rDNA gene sequencing, and examined intestinal pathological changes between control and IBS-like groups. The IBS-like group had significantly higher discharge amplitude of the external oblique muscle of the abdomen during colorectal distension (CRD) at 40- and 60 mmHg pressures. We observed differences in gut microbiota composition, with an increase in Bacteroidetes abundance and a decrease in Firmicutes in IBS-like rats. Beta-diversity analysis revealed the gut microbiota of the IBS-like group displayed higher consistent, while that of the control group exhibited substantial variation. Linear discriminant analysis effect size (LEfSe) detected 10 bacterial taxonomic clades showing statistically significant differences (7 increased and 3 decreased) in the IBS-like group. Functional analysis revealed that aminoacyl-tRNA biosynthesis and fatty acid biosynthesis were significantly altered, leading to changes in gene expression. Our findings demonstrate a definite correlation between gut microbiota dysbiosis and IBS during the male periadolescent period, with Alloprevotella and Bacteroide positively associated with high risk of IBS. The effects of specific bacterial genera may provide new insights for the development of treatments for IBS.
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Affiliation(s)
- Wei Lin
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Dongxiao Wu
- Department of Pediatrics, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Yongbin Zeng
- Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yuan Liu
- Cancer Research Center Nantong, Affiliated Tumor Hospital of Nantong University, China
| | - Dajie Yu
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Jianhang Wei
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yanliang Cai
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yueli Lin
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Bin Wu
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Huanhuan Huang
- Department of Pediatrics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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Lupu VV, Ghiciuc CM, Stefanescu G, Mihai CM, Popp A, Sasaran MO, Bozomitu L, Starcea IM, Adam Raileanu A, Lupu A. Emerging role of the gut microbiome in post-infectious irritable bowel syndrome: A literature review. World J Gastroenterol 2023; 29:3241-3256. [PMID: 37377581 PMCID: PMC10292139 DOI: 10.3748/wjg.v29.i21.3241] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/04/2023] [Accepted: 05/08/2023] [Indexed: 06/01/2023] Open
Abstract
Post-infectious irritable bowel syndrome (PI-IBS) is a particular type of IBS, with symptom onset after an acute episode of infectious gastroenteritis. Despite infectious disease resolution and clearance of the inciting pathogen agent, 10% of patients will develop PI-IBS. In susceptible individuals, the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota interactions. These changes can affect the gut-brain axis and the visceral sensitivity, disrupting the intestinal barrier, altering neuromuscular function, triggering persistent low inflammation, and sustaining the onset of IBS symptoms. There is no specific treatment strategy for PI-IBS. Different drug classes can be used to treat PI-IBS similar to patients with IBS in general, guided by their clinical symptoms. This review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS symptoms. It also discusses the current state of evidence on therapies targeting the microbiome in the management of PI-IBS. The results of microbial modulation strategies used in relieving IBS symptomatology are encouraging. Several studies on PI-IBS animal models reported promising results. However, published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are scarce. Future research is required.
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Affiliation(s)
- Vasile Valeriu Lupu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Cristina Mihaela Ghiciuc
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Gabriela Stefanescu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | | | - Alina Popp
- Faculty of General Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Maria Oana Sasaran
- Faculty of General Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu Mures 540142, Romania
| | - Laura Bozomitu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Iuliana Magdalena Starcea
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Anca Adam Raileanu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Ancuta Lupu
- Faculty of General Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
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31
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Goodoory VC, Ford AC. Antibiotics and Probiotics for Irritable Bowel Syndrome. Drugs 2023; 83:687-699. [PMID: 37184752 DOI: 10.1007/s40265-023-01871-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2023] [Indexed: 05/16/2023]
Abstract
Irritable bowel syndrome (IBS) is a disorder of a gut-brain interaction characterised by abdominal pain and a change in stool form or frequency. Current symptom-based definitions and the classification of IBS promote heterogeneity amongst patients, meaning that there may be several different pathophysiological abnormalities leading to similar symptoms. Although our understanding of IBS is incomplete, there are several indicators that the microbiome may be involved in a subset of patients. Techniques including a faecal sample analysis, colonic biopsies, duodenal aspirates or surrogate markers, such as breath testing, have been used to examine the gut microbiota in individuals with IBS. Because of a lack of a clear definition of what constitutes a healthy gut microbiota, and the fact that alterations in gut microbiota have only been shown to be associated with IBS, a causal relationship is yet to be established. We discuss several hypotheses as to how dysbiosis may be responsible for IBS symptoms, as well as potential treatment strategies. We review the current evidence for the use of antibiotics and probiotics to alter the microbiome in an attempt to improve IBS symptoms. Rifaximin, a non-absorbable antibiotic, is the most studied antibiotic and has now been licensed for use in IBS with diarrhoea in the USA, but the drug remains unavailable in many countries for this indication. Current evidence also suggests that certain probiotics, including Lactobacillus plantarum DSM 9843 and Bifidobacterium bifidum MIMBb75, may be efficacious in some patients with IBS. Finally, we describe the future challenges facing us in our attempt to modulate the microbiome to treat IBS.
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Affiliation(s)
- Vivek C Goodoory
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Room 125, 4th Floor, Bexley Wing, Beckett Street, Leeds, LS9 7TF, UK
| | - Alexander C Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.
- Leeds Gastroenterology Institute, St. James's University Hospital, Room 125, 4th Floor, Bexley Wing, Beckett Street, Leeds, LS9 7TF, UK.
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32
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Zhang F, Lau RI, Liu Q, Su Q, Chan FKL, Ng SC. Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications. Nat Rev Gastroenterol Hepatol 2023; 20:323-337. [PMID: 36271144 PMCID: PMC9589856 DOI: 10.1038/s41575-022-00698-4] [Citation(s) in RCA: 105] [Impact Index Per Article: 52.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/22/2022] [Indexed: 01/14/2023]
Abstract
The gastrointestinal tract is involved in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gut microbiota has important roles in viral entry receptor angiotensin-converting enzyme 2 (ACE2) expression, immune homeostasis, and crosstalk between the gut and lungs, the 'gut-lung axis'. Emerging preclinical and clinical studies indicate that the gut microbiota might contribute to COVID-19 pathogenesis and disease outcomes; SARS-CoV-2 infection was associated with altered intestinal microbiota and correlated with inflammatory and immune responses. Here, we discuss the cutting-edge evidence on the interactions between SARS-CoV-2 infection and the gut microbiota, key microbial changes in relation to COVID-19 severity and host immune dysregulations with the possible underlying mechanisms, and the conceivable consequences of the pandemic on the human microbiome and post-pandemic health. Finally, potential modulatory strategies of the gut microbiota are discussed. These insights could shed light on the development of microbiota-based interventions for COVID-19.
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Affiliation(s)
- Fen Zhang
- Microbiota I-Center (MagIC), Shatin, Hong Kong S.A.R., China
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
- State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
| | - Raphaela I Lau
- Microbiota I-Center (MagIC), Shatin, Hong Kong S.A.R., China
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
- State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
| | - Qin Liu
- Microbiota I-Center (MagIC), Shatin, Hong Kong S.A.R., China
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
- State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
| | - Qi Su
- Microbiota I-Center (MagIC), Shatin, Hong Kong S.A.R., China
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
- State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
| | - Francis K L Chan
- Microbiota I-Center (MagIC), Shatin, Hong Kong S.A.R., China
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
- State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China
| | - Siew C Ng
- Microbiota I-Center (MagIC), Shatin, Hong Kong S.A.R., China.
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China.
- State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China.
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Zhao Y, Zou DW. Gut microbiota and irritable bowel syndrome. J Dig Dis 2023; 24:312-320. [PMID: 37458142 DOI: 10.1111/1751-2980.13204] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 06/11/2023] [Accepted: 07/13/2023] [Indexed: 07/18/2023]
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain-gut-microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.
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Affiliation(s)
- Ye Zhao
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Duo Wu Zou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Konstantis G, Efstathiou S, Pourzitaki C, Kitsikidou E, Germanidis G, Chourdakis M. Efficacy and safety of probiotics in the treatment of irritable bowel syndrome: A systematic review and meta-analysis of randomised clinical trials using ROME IV criteria. Clin Nutr 2023; 42:800-809. [PMID: 37031468 DOI: 10.1016/j.clnu.2023.03.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 03/18/2023] [Accepted: 03/25/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder which affects a great number of patients globally. Clinical trials and meta-analyses have evaluated different therapies for IBS. Some of them have shown that probiotics play a significant role in the management of IBS-patients. Nevertheless, results are controversial, and the efficacy of the administration of probiotics remains to be confirmed, especially in regard to which type of probiotic-strains are beneficial. AIM The aim of the present meta-analysis is to assess the efficacy and safety of the administration of probiotics to IBS-patients with a diagnosis based on Rome IV criteria, which is performed for the first time. METHODS Electronic databases (Pubmed, Scopus and Cochrane) were searched until 26.01.2023 for randomized controlled trials (RCTs) studying the administration of probiotics in adult IBS-patients, who were categorized according to the Rome IV criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (ROB) 2.0. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcomes were the decrease of IBS-Symptom Severity Score (IBS-SSS) and decrease of abdominal pain. The secondary outcomes were the improvement in quality of life (QoL) and the decrease of bloating. Lastly, the adverse effects of probiotics were evaluated. The protocol of the study has been registered at protocols.io (DOI dx.doi.org/10.17504/protocols.io.14egn218yg5d/v1). RESULTS Six double-blind (N = 970) placebo-control RCTs fulfilled the inclusion criteria and overall, nine different strains of probiotics were examined. No significant reduction in IBS-SSS (WMD -43.2, 95% CI -87.5 to 1.0, I2 = 82.9%) was demonstrated, whereas a significant decrease regarding abdominal pain (SMD -0.94, 95% CI -1.53 to -0.35, I2 = 92,2) was shown. Furthermore, no correlation between improvement of QoL and the use of probiotics (SMD -0.64, 95% CI -1.27 to 0.00, I2 = 93,9%) was shown. However, probiotics were associated with a significant reduction in bloating (SMD -0.28, 95% CI -0.47 to -0.09, I2 = 36,0%). A qualitative synthesis was conducted about adverse events and showed that the use of probiotics' is safe without severe adverse events. CONCLUSIONS The administration of probiotics to IBS-patients demonstrated a positive effect on pain and bloating, but due to significant heterogeneity and confounding factors, that were not examined in the included studies, a definitive statement cannot be made. Moreover, probiotics did not lead to an improvement in other parameters. There is a need for larger RCTs in IBS-patients diagnosed according to Rome IV (not III) criteria and especially it is essential to be conducted RCTs which examine the administration of specific strains and have similar methodological characteristics.
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Affiliation(s)
- Georgios Konstantis
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Stylianos Efstathiou
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Chryssa Pourzitaki
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Elisavet Kitsikidou
- Department of Internal Medicine, Evangelical Hospital Dusseldorf, Dusseldorf, Germany
| | - Georgios Germanidis
- Division of Gastroenterology and Hepatology, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Pohl D, Vavricka S, Fox M, Madisch A, Studerus D, Wiesel P, Heinrich H, Linas I, Schoepfer A, Schwizer A, Wildi S. [Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice]. PRAXIS 2023; 112:304-316. [PMID: 37042398 DOI: 10.1024/1661-8157/a003988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/19/2023]
Abstract
Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice Abstract: Functional dyspepsia (FD) and irritable bowel syndrome (IBS), two common gastrointestinal entities with overlapping symptoms, should be diagnosed according to Rome IV criteria. This includes one or more of the following symptoms: in FD, postprandial fullness, early satiation, epigastric pain or burning; in IBS, recurrent abdominal pain associated with defecation, change in frequency of stool or form of stool. To exclude structural diseases, attention should be paid to alarm symptoms. As far as treatment is concerned, a stepwise scheme proves to be effective for both diseases. Step 1: doctor-patient discussion with explanation of diagnosis and prognosis as well as clarification of therapy goals; lifestyle adaptations; use of phytotherapeutics; step 2: symptom-oriented medication: for FD, PPIs or prokinetics; for IBS, antispasmodics, secretagogues, laxatives, bile acid sequestrants, antidiarrheals, antibiotics, probiotics; step 3: visceral analgesics (antidepressants).
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Affiliation(s)
- Daniel Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Schweiz
| | | | - Mark Fox
- Zentrum für Integrative Gastroenterologie, Klinik Arlesheim, Schweiz
| | | | | | - Paul Wiesel
- Gastro-entérologie, Centre Médical d'Epalinges, Epalinges, Schweiz
| | | | - Ioannis Linas
- Gastroenterologische Gruppenpraxis, Hirslanden Campus Bern, Schweiz
| | - Alain Schoepfer
- Service de gastro-entérologie et hépatologie, Centre hospitalier universitaire vaudois CHUV, Lausanne, Schweiz
| | - Alexandra Schwizer
- Klinik für Gastroenterologie und Hepatologie, Kantonsspital St. Gallen, St. Gallen, Schweiz
| | - Stephan Wildi
- Klinik für Gastroenterologie und Hepatologie, Kantonsspital St. Gallen, St. Gallen, Schweiz
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36
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Jalanka J, Gunn D, Singh G, Krishnasamy S, Lingaya M, Crispie F, Finnegan L, Cotter P, James L, Nowak A, Major G, Spiller RC. Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery. Gut 2023; 72:451-459. [PMID: 36171082 PMCID: PMC9933158 DOI: 10.1136/gutjnl-2021-326828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/14/2022] [Indexed: 12/08/2022]
Abstract
OBJECTIVES Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics. DESIGN A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40 days) as well as 40-60 days and >80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing. RESULTS PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria. CONCLUSION The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD. TRIAL REGISTRATION NUMBER NCT02040922.
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Affiliation(s)
- Jonna Jalanka
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK.,Human Microbiome Research Program, University of Helsinki Faculty of Medicine, Helsinki, Finland
| | - David Gunn
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Gulzar Singh
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Shanthi Krishnasamy
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK.,Department of Dietetics, Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia
| | - Melanie Lingaya
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Fiona Crispie
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Laura Finnegan
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Paul Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Louise James
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Adam Nowak
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Giles Major
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Robin C Spiller
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
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37
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Barbara G, Cremon C, Bellini M, Corsetti M, Di Nardo G, Falangone F, Fuccio L, Galeazzi F, Iovino P, Sarnelli G, Savarino EV, Stanghellini V, Staiano A, Stasi C, Tosetti C, Turco R, Ubaldi E, Zagari RM, Zenzeri L, Marasco G. Italian guidelines for the management of irritable bowel syndrome: Joint Consensus from the Italian Societies of: Gastroenterology and Endoscopy (SIGE), Neurogastroenterology and Motility (SINGEM), Hospital Gastroenterologists and Endoscopists (AIGO), Digestive Endoscopy (SIED), General Medicine (SIMG), Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP) and Pediatrics (SIP). Dig Liver Dis 2023; 55:187-207. [PMID: 36517261 DOI: 10.1016/j.dld.2022.11.015] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/21/2022] [Accepted: 11/24/2022] [Indexed: 01/29/2023]
Abstract
The irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction. IBS is still associated with areas of uncertainties, especially regarding the optimal diagnostic work-up and the more appropriate management. Experts from 7 Italian Societies conducted a Delphi consensus with literature summary and voting process on 27 statements. Recommendations and quality of evidence were evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was defined as >80% agreement and reached for all statements. In terms of diagnosis, the consensus supports a positive diagnostic strategy with a symptom-based approach, including the psychological comorbidities assessment and the exclusion of alarm symptoms, together with the digital rectal examination, full blood count, C-reactive protein, serology for coeliac disease, and fecal calprotectin assessment. Colonoscopy should be recommended in patients with alarm features. Regarding treatment, the consensus strongly supports a dietary approach for patients with IBS, the use of soluble fiber, secretagogues, tricyclic antidepressants, psychologically directed therapies and, only in specific IBS subtypes, rifaximin. A conditional recommendation was achieved for probiotics, polyethylene glycol, antispasmodics, selective serotonin reuptake inhibitors and, only in specific IBS subtypes, 5-HT3 antagonists, 5-HT4 agonists, bile acid sequestrants.
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Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Sciences and New Technologies in Medicine and Surgery, University of Pisa, 56010 Pisa, Italy
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham Digestive Diseases Biomedical Research Centre, Nottingham, United Kingdom
| | - Giovanni Di Nardo
- NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| | - Francesca Falangone
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Sapienza, Rome, Italy
| | - Lorenzo Fuccio
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy
| | - Francesca Galeazzi
- Gastroenterology Unit, Azienda Ospedale Università di Padova, 35128 Padua, Italy
| | - Paola Iovino
- Gastrointestinal Unit Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy
| | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | | | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Annamaria Staiano
- Department of Translational Medical Sciences-Section of Pediatric, University Federico II, 80100 Naples, Italy
| | - Cristina Stasi
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | | | - Rossella Turco
- Department of Translational Medical Sciences-Section of Pediatric, University Federico II, 80100 Naples, Italy
| | - Enzo Ubaldi
- Primary Care, Health Care Agency of Ascoli Piceno, Ascoli Piceno, Italy
| | - Rocco Maurizio Zagari
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy
| | - Letizia Zenzeri
- NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero Universitaria di Bologna, 40126 Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
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38
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Brierley SM, Greenwood-Van Meerveld B, Sarnelli G, Sharkey KA, Storr M, Tack J. Targeting the endocannabinoid system for the treatment of abdominal pain in irritable bowel syndrome. Nat Rev Gastroenterol Hepatol 2023; 20:5-25. [PMID: 36168049 DOI: 10.1038/s41575-022-00682-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/16/2022] [Indexed: 12/27/2022]
Abstract
The management of visceral pain in patients with disorders of gut-brain interaction, notably irritable bowel syndrome, presents a considerable clinical challenge, with few available treatment options. Patients are increasingly using cannabis and cannabinoids to control abdominal pain. Cannabis acts on receptors of the endocannabinoid system, an endogenous system of lipid mediators that regulates gastrointestinal function and pain processing pathways in health and disease. The endocannabinoid system represents a logical molecular therapeutic target for the treatment of pain in irritable bowel syndrome. Here, we review the physiological and pathophysiological functions of the endocannabinoid system with a focus on the peripheral and central regulation of gastrointestinal function and visceral nociception. We address the use of cannabinoids in pain management, comparing them to other treatment modalities, including opioids and neuromodulators. Finally, we discuss emerging therapeutic candidates targeting the endocannabinoid system for the treatment of pain in irritable bowel syndrome.
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Affiliation(s)
- Stuart M Brierley
- Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia
- Hopwood Centre for Neurobiology, Lifelong Health, South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, Australia
| | | | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Keith A Sharkey
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
| | - Martin Storr
- Department of Medicine, Ludwig-Maximilians University, Munich, Germany
- Zentrum für Endoskopie, Starnberg, Germany
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
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39
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Yao C, Li Y, Luo L, Xie F, Xiong Q, Li T, Yang C, Feng PM. Significant Differences in Gut Microbiota Between Irritable Bowel Syndrome with Diarrhea and Healthy Controls in Southwest China. Dig Dis Sci 2023; 68:106-127. [PMID: 35503487 DOI: 10.1007/s10620-022-07500-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 03/24/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a heterogeneous disease, which is closely related to environmental factors and gut microbiota. OBJECTIVE To study gut microbiota in IBS-D of Han nationality in Southwest China and explore its relationship with environmental factors. METHODS One hundred and twenty cases of IBS-D and 63 cases of HCs were recruited; baseline data such as age, height, and weight were collected. HAMA, HAMD, IBS-SSS, IBS-QOL, and laboratory tests were performed. Feces were collected for 16S rDNA sequencing. Then, the differences of gut microbiota were analyzed and looked for biomarkers of each. FAPROTAX was used to predict the functional differences of gut microbiota. Spearman analysis was conducted between the phylum level and environmental factor. RESULTS There were significant differences in daily life between IBS-D and HCs, especially in the spicy taste. The scores of HAMA and HAMD, urea, and transaminase in IBS-D were significantly higher than those of HCs. The richness of gut microbiota in IBS-D was significantly lower than that of HCs, as well as the beta diversity, but not diversity. The biomarkers of IBS-D were Prevotella, Clostridiales, and Roseburia, and the biomarkers of HCs were Veillonellaceae, Bacteroides coprocola, and Bifidobacteriales. The functions of gut microbiota in IBS-D were significantly different from HCs. Correlation analysis showed that multiple gut microbiota were closely related to HAMA, IBS-SSS, IBS-QOL, inflammatory indexes, and liver enzymes. CONCLUSION There are significant differences in richness of gut microbiota, flora structure, and flora function between IBS-D and HCs in Southwest China. These differences may be closely related to environmental factors such as eating habits, living habits, and mental and psychological factors. CLINICAL TRIAL REGISTRATION The trial was registered and approved in China Clinical Trial Registry (Registration No. ChiCTR2100045751).
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Affiliation(s)
- Chengjiao Yao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China.,Department of Geriatrics of the Affiliated Hospital, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yilin Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China.,North Sichuan Medical College, Nanchong, Sichuan, China
| | - Lihong Luo
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China
| | - Fengjiao Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China
| | - Qin Xiong
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China
| | - Tinglin Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China
| | - Chunrong Yang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China
| | - Pei-Min Feng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, Sichuan, China.
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40
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Lynch CMK, O’Riordan KJ, Clarke G, Cryan JF. Gut Microbes: The Gut Brain Connection. CLINICAL UNDERSTANDING OF THE HUMAN GUT MICROBIOME 2023:33-59. [DOI: 10.1007/978-3-031-46712-7_4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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41
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Chi ZC. Progress in research of low-grade inflammation in irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2022; 30:1051-1065. [DOI: 10.11569/wcjd.v30.i24.1051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common intestinal disease with a prevalence of 10%-15%. However, its pathophysiology is still not completely clear, and it has long been considered as a functional disease. In recent years, it has been found that low-grade inflammation plays a pathogenic role in IBS. Studies have confirmed that there is persistent mucosal inflammation at the microscopic and molecular levels. This review discusses the evidence, role, and clinical relevance of mucosal inflammation in IBS. In addition to mucosal inflammation, neuroinflammation may lead to changes in neuroendocrine pathways and glucocorticoid receptor genes through the "gut-brain" axis, and thus cause IBS through proinflammatory phenotype and hypothalamic pituitary adrenal axis and 5-hydroxytryptamine dysfunction. The observation that IBS patients can benefit from anti-inflammatory therapy also confirms that IBS is associated with inflammation.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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42
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Zhang W, Wan Z, Li X, Li R, Luo L, Song Z, Miao Y, Li Z, Wang S, Shan Y, Li Y, Chen B, Zhen H, Sun Y, Fang M, Ding J, Yan Y, Zong Y, Wang Z, Zhang W, Yang H, Yang S, Wang J, Jin X, Wang R, Chen P, Min J, Zeng Y, Li T, Xu X, Nie C. A population-based study of precision health assessments using multi-omics network-derived biological functional modules. Cell Rep Med 2022; 3:100847. [PMID: 36493776 PMCID: PMC9798030 DOI: 10.1016/j.xcrm.2022.100847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 10/05/2022] [Accepted: 11/11/2022] [Indexed: 12/13/2022]
Abstract
Recent technological advances in multi-omics and bioinformatics provide an opportunity to develop precision health assessments, which require big data and relevant bioinformatic methods. Here we collect multi-omics data from 4,277 individuals. We calculate the correlations between pairwise features from cross-sectional data and then generate 11 biological functional modules (BFMs) in males and 12 BFMs in females using a community detection algorithm. Using the features in the BFM associated with cardiometabolic health, carotid plaques can be predicted accurately in an independent dataset. We developed a model by comparing individual data with the health baseline in BFMs to assess health status (BFM-ash). Then we apply the model to chronic patients and modify the BFM-ash model to assess the effects of consuming grape seed extract as a dietary supplement. Finally, anomalous BFMs are identified for each subject. Our BFMs and BFM-ash model have huge prospects for application in precision health assessment.
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Affiliation(s)
- Wei Zhang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Ziyun Wan
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Xiaoyu Li
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,BGI Education Center, University of the Chinese Academy of Sciences, Shenzhen 518083, China
| | - Rui Li
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Lihua Luo
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,BGI Education Center, University of the Chinese Academy of Sciences, Shenzhen 518083, China
| | - Zijun Song
- The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yu Miao
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,BGI Education Center, University of the Chinese Academy of Sciences, Shenzhen 518083, China
| | - Zhiming Li
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Shiyu Wang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,BGI Education Center, University of the Chinese Academy of Sciences, Shenzhen 518083, China
| | - Ying Shan
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Yan Li
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Bangwei Chen
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
| | - Hefu Zhen
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Yuzhe Sun
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Mingyan Fang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Jiahong Ding
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Yizhen Yan
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Yang Zong
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Zhen Wang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Wenwei Zhang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Huanming Yang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,James D. Watson Institute of Genome Sciences, Hangzhou 310058, China
| | - Shuang Yang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Jian Wang
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,James D. Watson Institute of Genome Sciences, Hangzhou 310058, China
| | - Xin Jin
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Ru Wang
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, China
| | - Peijie Chen
- School of Exercise and Health, Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai, China
| | - Junxia Min
- The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yi Zeng
- Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, China
| | - Tao Li
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Xun Xu
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China
| | - Chao Nie
- BGI-Shenzhen, Shenzhen 518083, China,China National GeneBank, Shenzhen 518120, China,Corresponding author
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43
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Relationship between mucosa-associated gut microbiota and human diseases. Biochem Soc Trans 2022; 50:1225-1236. [PMID: 36214382 PMCID: PMC9704521 DOI: 10.1042/bst20201201] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 09/21/2022] [Accepted: 09/23/2022] [Indexed: 11/17/2022]
Abstract
The mucus layer covering the gastrointestinal (GI) tract plays a critical role in maintaining gut homeostasis. In the colon, the inner mucus layer ensures commensal microbes are kept at a safe distance from the epithelium while mucin glycans in the outer mucus layer provide microbes with nutrients and binding sites. Microbes residing in the mucus form part of the so-called 'mucosa-associated microbiota' (MAM), a microbial community which, due to its close proximity to the epithelium, has a profound impact on immune and metabolic health by directly impacting gut barrier function and the immune system. Alterations in GI microbial communities have been linked to human diseases. Although most of this knowledge is based on analysis of the faecal microbiota, a growing number of studies show that the MAM signature differs from faecal or luminal microbiota and has the potential to be used to distinguish between diseased and healthy status in well-studied conditions such as IBD, IBS and CRC. However, our knowledge about spatial microbial alterations in pathogenesis remains severely hampered by issues surrounding access to microbial communities in the human gut. In this review, we provide state-of-the-art information on how to access MAM in humans, the composition of MAM, and how changes in MAM relate to changes in human health and disease. A better understanding of interactions occurring at the mucosal surface is essential to advance our understanding of diseases affecting the GI tract and beyond.
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44
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Nakamura Y, Suzuki S, Murakami S, Nishimoto Y, Higashi K, Watarai N, Umetsu J, Ishii C, Ito Y, Mori Y, Kohno M, Yamada T, Fukuda S. Integrated gut microbiome and metabolome analyses identified fecal biomarkers for bowel movement regulation by Bifidobacterium longum BB536 supplementation: A RCT. Comput Struct Biotechnol J 2022; 20:5847-5858. [PMID: 36382178 PMCID: PMC9636538 DOI: 10.1016/j.csbj.2022.10.026] [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: 04/11/2022] [Revised: 10/19/2022] [Accepted: 10/19/2022] [Indexed: 11/03/2022] Open
Abstract
Background Bifidobacterium longum BB536 supplementation can be used to regulate bowel movements in various people, including healthy subjects and patients with irritable bowel syndrome (IBS); however, individuals vary in their responses to B. longum BB536 treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates the effects of diet or drugs on the host. Here, we investigated intestinal features, such as the microbiome and metabolome, related to B. longum BB536 effectiveness in increasing bowel movement frequency. Results A randomized, double-blind controlled crossover trial was conducted with 24 adults who mainly tended to be constipated. The subjects received a two-week dietary intervention consisting of B. longum BB536 in acid-resistant seamless capsules or similarly encapsulated starch powder as the placebo control. Bowel movement frequency was recorded daily, and fecal samples were collected at several time points, and analyzed by metabologenomic approach that consists of an integrated analysis of metabolome data obtained using mass spectrometry and microbiome data obtained using high-throughput sequencing. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predicted by machine learning based on the microbiome and metabolome features of the fecal samples collected before B. longum intake. The abundances of eight bacterial genera were significantly different between responders and nonresponders. Conclusions Intestinal microbiome and metabolome profiles might be utilized as potential markers of improved bowel movement after B. longum BB536 supplementation. These findings have implications for the development of personalized probiotic treatments.
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Key Words
- 16S rRNA gene sequence
- AUROC, area under the receiver operating characteristic curve
- Bifidobacteria
- CE-TOFMS, capillary electrophoresis time-of-flight mass spectrometry
- CSA, D-camphor-10-sulfonic acid
- ESVs, exact sequence variants
- FDR, false discovery rate
- Gut microbiota
- IBD, inflammatory bowel disease
- IBS, irritable bowel syndrome
- ITT, intention-to-treat
- MCMC, Markov Chain Monte Carlo
- MDS, multidimensional scaling
- Machine learning
- Metabologenomics
- NRs, nonresponders
- PP, per-protocol population
- PSRF, potential scale reduction factor
- Probiotics
- SCFAs, short-chain fatty acids
- SRs, strong responders
- WAIC, Widely Applicable Information Criterion
- WRs, weak responders
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Affiliation(s)
- Yuya Nakamura
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Shinya Suzuki
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
- Education Academy of Computational Life Science (ACLS), 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Shinnosuke Murakami
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | | | - Koichi Higashi
- National Institute of Genetics, Genome Evolution Laboratory, Yata 1111, Mishima 411-8540, Japan
| | - Naoki Watarai
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Junpei Umetsu
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Chiharu Ishii
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | - Yutaro Ito
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | - Yuka Mori
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | - Mamiko Kohno
- MORISHITA JINTAN CO., LTD, Health Care Product Department, Research & Development Division, 1-2-40 Tamatsukuri, Chuo-ku, Osaka 540-8566, Japan
| | - Takuji Yamada
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Shinji Fukuda
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Transborder Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan
- Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Hongo, Tokyo 113-8421, Japan
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45
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Ma W, Drew DA, Staller K. The Gut Microbiome and Colonic Motility Disorders: A Practical Framework for the Gastroenterologist. Curr Gastroenterol Rep 2022; 24:115-126. [PMID: 35943661 PMCID: PMC10039988 DOI: 10.1007/s11894-022-00847-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2022] [Indexed: 10/15/2022]
Abstract
PURPOSE OF REVIEW Colonic motility disorders may be influenced by the gut microbiota, which plays a role in modulating sensory and motor function. However, existing data are inconsistent, possibly due to complex disease pathophysiology, fluctuation in symptoms, and difficulty characterizing high-resolution taxonomic composition and function of the gut microbiome. RECENT FINDINGS Increasingly, human studies have reported associations between gut microbiome features and colonic motility disorders, such as irritable bowel syndrome and constipation. Several microbial metabolites have been identified as regulators of colonic motility in animal models. Modulation of the gut microbiota via dietary intervention, probiotics, and fecal microbiota transplant is a promising avenue for treatment for these diseases. An integration of longitudinal multi-omics data will facilitate further understanding of the causal effects of dysbiosis on disease. Further understanding of the microbiome-driven mechanisms underlying colonic motility disorders may be leveraged to develop personalized, microbiota-based approaches for disease prevention and treatment.
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Affiliation(s)
- Wenjie Ma
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114-2696, Boston, MA, United States
| | - David A Drew
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114-2696, Boston, MA, United States
| | - Kyle Staller
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114-2696, Boston, MA, United States.
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Blackett JW, Sun Y, Purpura L, Margolis KG, Elkind MS, O'Byrne S, Wainberg M, Abrams JA, Wang HH, Chang L, Freedberg DE. Decreased Gut Microbiome Tryptophan Metabolism and Serotonergic Signaling in Patients With Persistent Mental Health and Gastrointestinal Symptoms After COVID-19. Clin Transl Gastroenterol 2022; 13:e00524. [PMID: 36049050 PMCID: PMC9624499 DOI: 10.14309/ctg.0000000000000524] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 08/10/2022] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION An estimated 15%-29% of patients report new gastrointestinal (GI) symptoms after coronavirus-19 disease (COVID-19) while 4%-31% report new depressive symptoms. These symptoms may be secondary to gut microbiome tryptophan metabolism and 5-hydroxytryptamine (5-HT)-based signaling. METHODS This study used specimens from 2 patient cohorts: (i) fecal samples from patients with acute COVID-19 who participated in a randomized controlled trial testing prebiotic fiber and (ii) blood samples from patients with acute COVID-19. Six months after recovering from COVID-19, both cohorts answered questions related to GI symptoms and anxiety or depression. Microbiome composition and function, focusing on tryptophan metabolism-associated pathways, and plasma 5-HT were assessed. RESULTS In the first cohort (n = 13), gut microbiome L-tryptophan biosynthesis during acute COVID-19 was decreased among those who developed more severe GI symptoms (2.0-fold lower log activity comparing those with the most severe GI symptoms vs those with no symptoms, P = 0.06). All tryptophan pathways showed decreased activity among those with more GI symptoms. The same pathways were also decreased in those with the most severe mental health symptoms after COVID-19. In an untargeted analysis, 5 additional metabolic pathways significantly differed based on subsequent development of GI symptoms. In the second cohort (n = 39), plasma 5-HT concentration at the time of COVID-19 was increased 5.1-fold in those with GI symptoms alone compared with those with mental health symptoms alone ( P = 0.02). DISCUSSION Acute gut microbiome-mediated reduction in 5-HT signaling may contribute to long-term GI and mental health symptoms after COVID-19. Future studies should explore modification of 5-HT signaling to reduce post-COVID symptoms.
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Affiliation(s)
- John W. Blackett
- Division of Digestive and Liver Diseases, Mayo Clinic, Rochester, Minnesota, USA
| | - Yiwei Sun
- Program in Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA
- Department of Systems Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Lawrence Purpura
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, New York, USA
| | - Kara Gross Margolis
- Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
- Columbia University Digestive and Liver Diseases Research Center New York, New York, USA
| | - Mitchell S.V. Elkind
- Department of Neurology, Vagelos College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
| | - Sheila O'Byrne
- Columbia University Digestive and Liver Diseases Research Center New York, New York, USA
| | - Milton Wainberg
- Department of Psychiatry, Columbia University Irving Medical Center and the New York State Psychiatric Institute; New York, New York, USA
| | - Julian A. Abrams
- Columbia University Digestive and Liver Diseases Research Center New York, New York, USA
- Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, New York, USA
| | - Harris H. Wang
- Department of Systems Biology, Columbia University Irving Medical Center, New York, New York, USA
- Columbia University Digestive and Liver Diseases Research Center New York, New York, USA
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases and G. Oppenheimer Center for Neurobiology of Stress and Resilience, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Daniel E. Freedberg
- Columbia University Digestive and Liver Diseases Research Center New York, New York, USA
- Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, New York, USA
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Lv L, Ruan G, Ping Y, Cheng Y, Tian Y, Xiao Z, Zhao X, Chen D, Wei Y. Clinical study on sequential treatment of severe diarrhea irritable bowel syndrome with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules. Front Cell Infect Microbiol 2022; 12:1025889. [PMID: 36250045 PMCID: PMC9555570 DOI: 10.3389/fcimb.2022.1025889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 09/12/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To study the effect of precision probiotic strains transplantation capsules on diarrhea irritable bowel syndrome compared with fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules. Methods Two patients with severe irritable bowel syndrome were treated with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules in sequence. IBS-SSS, IBS-QoL, GSRS, stool frequency, stool character, degree of abdominal pain, GAD-7, and PHQ9 scores of patients at 0, 2, 4, 6, 8, 10, and 12 weeks of treatment were monitored and recorded, and stool samples were collected for metagenomics and metabolomics. Results It was found that the IBS-SSS score of patient case 1 decreased by 175 points and that of patient case 2 decreased by 100 points after treatment of precision probiotic strains transplantation capsules. There was no significant decrease after fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules were used. At the same time, compared with fecal microbiota transplantation and live combined bacillus subtilis and enterococcus faecium capsules, the IBS QoL, stool frequency, stool character, degree of abdominal pain and GAD-7 score of patient case 1 improved more significantly by the precision probiotic strains transplantation capsules. And the stool frequency and stool character score of patient case 2 decreased more significantly. Intestinal microbiota also improved more significantly after the precise capsule transplantation treatment. And we found Eubacterium_ Eligens showed the same change trend in the treatment of two patients, which may play a role in the treatment. Conclusion precision probiotic strains transplantation capsules is more beneficial to improve the intestinal microbiota of patients than microbiota transplantation capsule and live combined bacillus subtilis and enterococcus faecium capsules, so as to better alleviate clinical symptoms. This study provides a more perfect and convenient therapeutic drugs for the treatment of IBS.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Yanling Wei
- *Correspondence: Dongfeng Chen, ; Yanling Wei,
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Liu H, Zhang B, Li F, Liu L, Li F. Shifts in the intestinal microflora of meat rabbits in response to glucocorticoids. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2022; 102:5422-5428. [PMID: 35338488 DOI: 10.1002/jsfa.11895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 01/04/2022] [Accepted: 03/25/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND As major stress hormones, glucocorticoids can directly or indirectly affect the intestinal microflora, although few studies have focused on changes in the composition of the intestinal microflora. In this study, rabbits were randomly divided into two groups: gavage administration with saline, and the same doses of dexamethasone (1 mg kg-1 ). After 7 days, the microbial diversity of the jejunum contents was analysed. RESULTS The gut microflora richness and diversity had no significant difference between the two groups. The proportions of Firmicutes and Bacteroidetes were the most abundant in the jejunum of meat rabbits. Dexamethasone injection led to a change in the structure of the gut microflora composition, and we found that there were six biomarkers with linear discriminant analysis score >4 (Firmicutes, Caproiciproducens, Clostridiales, Clostridia, Psychrobacter, and Psychrobacter faecalis), moreover, the results of this study provide new insight into alleviating the effects of stress on meat rabbits. CONCLUSION It was concluded that glucocorticoids caused changes in the composition of intestinal microflora. © 2022 Society of Chemical Industry.
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Affiliation(s)
- Hongli Liu
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Technology, Shandong Agricultural University, Taian, China
- Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation, Department of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, China
| | - Bin Zhang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Technology, Shandong Agricultural University, Taian, China
| | - Fan Li
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Technology, Shandong Agricultural University, Taian, China
| | - Lei Liu
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Technology, Shandong Agricultural University, Taian, China
| | - Fuchang Li
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Science and Technology, Shandong Agricultural University, Taian, China
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Iribarren C, Maasfeh L, Öhman L, Simrén M. Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2022; 3:e7. [PMID: 39295774 PMCID: PMC11406401 DOI: 10.1017/gmb.2022.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 06/02/2022] [Accepted: 07/26/2022] [Indexed: 09/21/2024]
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a complex pathophysiology. Growing evidence suggests that alterations of the gut microenvironment, including microbiota composition and function, may be involved in symptom generation. Therefore, attempts to modulate the gut microenvironment have provided promising results as an indirect approach for IBS management. Antibiotics, probiotics, prebiotics, food and faecal microbiota transplantation are the main strategies for alleviating IBS symptom severity by modulating gut microbiota composition and function (eg. metabolism), gut barrier integrity and immune activity, although with varying efficacy. In this narrative review, we aim to provide an overview of the current approaches targeting the gut microenvironment in order to indirectly manage IBS symptoms.
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Affiliation(s)
- Cristina Iribarren
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lujain Maasfeh
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA
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Biazzo M, Deidda G. Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases. J Clin Med 2022; 11:jcm11144119. [PMID: 35887883 PMCID: PMC9320118 DOI: 10.3390/jcm11144119] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/08/2022] [Accepted: 07/12/2022] [Indexed: 02/01/2023] Open
Abstract
The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.
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Affiliation(s)
- Manuele Biazzo
- The BioArte Limited, Life Sciences Park, Triq San Giljan, SGN 3000 San Gwann, Malta;
- SienabioACTIVE, University of Siena, Via Aldo Moro 1, 53100 Siena, Italy
| | - Gabriele Deidda
- Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy
- Correspondence: ; Tel.: +39-049-827-6125
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