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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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Lu D, Ma X, Tao K, Lei H. Advancements in the Pathogenesis, Diagnosis, and Therapeutic Implications of Intestinal Bacteria. Curr Issues Mol Biol 2025; 47:106. [PMID: 39996827 PMCID: PMC11853859 DOI: 10.3390/cimb47020106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/28/2025] [Accepted: 02/06/2025] [Indexed: 02/26/2025] Open
Abstract
Intestinal bacteria form one of the most complex microbial communities in the human body, playing a crucial role in maintaining host health and contributing to the development of various diseases. Here, we provide a comprehensive overview of the composition and function of intestinal bacteria, the factors affecting their homeostasis, and their association and mechanisms with a range of diseases (e.g., inflammatory bowel diseases, colorectal cancer, metabolic diseases). Additionally, their advanced potential in disease diagnosis and treatment is highlighted. Therapies, such as chemotherapy, radiotherapy, and immunotherapy, are significantly impacted by intestinal bacteria, with research indicating that bacteria can enhance chemoimmunotherapy efficiency by affecting T cell recruitment and immune cell infiltration. Fecal microbiota transplantation has emerged as a promising option for treating recurrent Clostridium difficile infections and certain metabolic and neurological disorders. Gut bacteria-related serum metabolites serve as non-invasive indicators for diagnosing CRC, while fecal immunochemical tests offer promising applications in CRC screening. Future research is needed to better understand the causal relationships between intestinal bacteria and diseases, develop more precise diagnostic tools, and evaluate the effectiveness and safety of microbiome-targeted therapies in clinical treatment. This study provides deeper insights into the role of intestinal bacteria in human health and disease, providing a scientific basis for innovative therapeutic strategies that have the potential to transform the landscape of healthcare.
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Affiliation(s)
| | | | - Kaixiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (D.L.); (X.M.)
| | - Hongwei Lei
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (D.L.); (X.M.)
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Nishijima S, Stankevic E, Aasmets O, Schmidt TSB, Nagata N, Keller MI, Ferretti P, Juel HB, Fullam A, Robbani SM, Schudoma C, Hansen JK, Holm LA, Israelsen M, Schierwagen R, Torp N, Telzerow A, Hercog R, Kandels S, Hazenbrink DHM, Arumugam M, Bendtsen F, Brøns C, Fonvig CE, Holm JC, Nielsen T, Pedersen JS, Thiele MS, Trebicka J, Org E, Krag A, Hansen T, Kuhn M, Bork P. Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations. Cell 2025; 188:222-236.e15. [PMID: 39541968 DOI: 10.1016/j.cell.2024.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 07/12/2024] [Accepted: 10/14/2024] [Indexed: 11/17/2024]
Abstract
The microbiota in individual habitats differ in both relative composition and absolute abundance. While sequencing approaches determine the relative abundances of taxa and genes, they do not provide information on their absolute abundances. Here, we developed a machine-learning approach to predict fecal microbial loads (microbial cells per gram) solely from relative abundance data. Applying our prediction model to a large-scale metagenomic dataset (n = 34,539), we demonstrated that microbial load is the major determinant of gut microbiome variation and is associated with numerous host factors, including age, diet, and medication. We further found that for several diseases, changes in microbial load, rather than the disease condition itself, more strongly explained alterations in patients' gut microbiome. Adjusting for this effect substantially reduced the statistical significance of the majority of disease-associated species. Our analysis reveals that the fecal microbial load is a major confounder in microbiome studies, highlighting its importance for understanding microbiome variation in health and disease.
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Affiliation(s)
- Suguru Nishijima
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Evelina Stankevic
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Oliver Aasmets
- Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Thomas S B Schmidt
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Naoyoshi Nagata
- Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
| | - Marisa Isabell Keller
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Pamela Ferretti
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Helene Bæk Juel
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Anthony Fullam
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | | | - Christian Schudoma
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johanne Kragh Hansen
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Louise Aas Holm
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
| | - Mads Israelsen
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Robert Schierwagen
- Department of Internal Medicine B, University of Münster, Münster, Germany
| | - Nikolaj Torp
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Anja Telzerow
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Rajna Hercog
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Stefanie Kandels
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Diënty H M Hazenbrink
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Manimozhiyan Arumugam
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Charlotte Brøns
- Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Cilius Esmann Fonvig
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens-Christian Holm
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Trine Nielsen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Medical department, University Hospital Zeeland, Køge, Denmark
| | - Julie Steen Pedersen
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Maja Sofie Thiele
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Münster, Germany; European Foundation for the Study of Chronic Liver Failure, EFCLIF, Barcelona, Spain
| | - Elin Org
- Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Aleksander Krag
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Michael Kuhn
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
| | - Peer Bork
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany; Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany.
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García Mansilla MJ, Rodríguez Sojo MJ, Lista AR, Ayala Mosqueda CV, Ruiz Malagón AJ, Gálvez J, Rodríguez Nogales A, Rodríguez Sánchez MJ. Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential Therapeutic Effects of Probiotics and Their Metabolites. Nutrients 2024; 17:155. [PMID: 39796588 PMCID: PMC11723002 DOI: 10.3390/nu17010155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
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Affiliation(s)
- María José García Mansilla
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
| | - María Jesús Rodríguez Sojo
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - Andrea Roxana Lista
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | | | - Antonio Jesús Ruiz Malagón
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Málaga, Spain
| | - Julio Gálvez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
- CIBER de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alba Rodríguez Nogales
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - María José Rodríguez Sánchez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
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Procházková N, Laursen MF, La Barbera G, Tsekitsidi E, Jørgensen MS, Rasmussen MA, Raes J, Licht TR, Dragsted LO, Roager HM. Gut physiology and environment explain variations in human gut microbiome composition and metabolism. Nat Microbiol 2024; 9:3210-3225. [PMID: 39604623 PMCID: PMC11602727 DOI: 10.1038/s41564-024-01856-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: 12/13/2023] [Accepted: 10/11/2024] [Indexed: 11/29/2024]
Abstract
The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.
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Affiliation(s)
- Nicola Procházková
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Martin F Laursen
- National Food Institute, Technical University of Denmark, Kgs Lyngby, Denmark
| | - Giorgia La Barbera
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Eirini Tsekitsidi
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Malte S Jørgensen
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Morten A Rasmussen
- Department of Food Science, University of Copenhagen, Frederiksberg, Denmark
- Copenhagen Studies on Asthma in Childhood (COPSAC), Herlev-Gentofte Hospital, University of Copenhagen, Gentofte, Denmark
| | - Jeroen Raes
- Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium
- Center for Microbiology, VIB, Leuven, Belgium
| | - Tine R Licht
- National Food Institute, Technical University of Denmark, Kgs Lyngby, Denmark
| | - Lars O Dragsted
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Henrik M Roager
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark.
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Chen XL, Jiang MZ. [Research progress of metabolomics in children with irritable bowel syndrome]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2024; 26:989-994. [PMID: 39267517 PMCID: PMC11404471 DOI: 10.7499/j.issn.1008-8830.2404130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by symptoms such as abdominal pain, diarrhea, constipation, and indigestion. Given its unclear etiology and pathogenesis, and the absence of specific biomarkers, clinical diagnosis and treatment of IBS continue to pose significant challenges. In recent years, metabolomics technology, known for its non-invasive, high-throughput, high-precision, and highly reproducible features, has been widely applied in the diagnosis, treatment, and prognosis of various diseases. Therefore, metabolomics technology is expected to offer novel insights and methodologies for the biological mechanism research, diagnosis, and treatment of IBS. This article reviews recent advancements in the application of metabolomics to IBS, exploring its potential value in the clinical diagnosis and treatment of children with this condition.
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Affiliation(s)
- Xiao-Long Chen
- Department of Gastroenterology and Pediatric Endoscopy Center, Children's Hospital, Zhejiang University School of Medicine/National Clinical Research Center for Child Health/National Children's Regional Medical Center, Hangzhou 310052, China
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7
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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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Shin A, Xing Y, Waseem MR, Siwiec R, James-Stevenson T, Rogers N, Bohm M, Wo J, Lockett C, Gupta A, Kadariya J, Toh E, Anderson R, Xu H, Gao X. Microbiota-Short Chain Fatty Acid Relationships Underlie Clinical Heterogeneity and Identify Key Microbial Targets in Irritable Bowel Syndrome (IBS). MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.01.31.24302084. [PMID: 38352442 PMCID: PMC10863002 DOI: 10.1101/2024.01.31.24302084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/27/2024]
Abstract
Background Identifying microbial targets in irritable bowel syndrome (IBS) and other disorders of gut-brain interaction (DGBI) is challenging due to the dynamic nature of microbiota-metabolite-host interactions. SCFA are key microbial metabolites that modulate intestinal homeostasis and may influence IBS pathophysiology. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features varied across IBS subtypes and endophenotypes. Among 96 participants who were screened, 71 completed the study. We conducted in-depth investigations of stool microbial metagenomes, stool SCFA, and measurable IBS traits (stool bile acids, colonic transit, stool form) in 41 patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and 17 healthy controls. We used partial canonical correspondence analyses (pCCA), conditioned on transit, to quantify microbe-SCFA associations across clinical groups. To explore relationships between microbially-derived SCFA and IBS traits, we compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by their stool characteristics as well as stool microbiomes of patients with and without clinical bile acid malabsorption. Results Overall stool microbiome composition and individual taxa abundances differed between clinical groups. Microbes-SCFA associations differed across groups and revealed key taxa including Dorea sp. CAG:317 and Bifidobacterium pseudocatenulatum in IBS-D and Akkermansia muciniphila and Prevotella copri in IBS-C that that may drive subtype-specific microbially-mediated mechanisms. Strongest microbe-SCFA associations were observed in IBS-D and several SCFA-producing species surprisingly demonstrated inverse correlations with SCFA. Fewer bacterial taxa were associated with acetate to butyrate ratios in IBS compared to health. In participants selected by stool form, we demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D patients with BAM. Conclusion Keystone taxa responsible for SCFA production differ according to IBS subtype and traits and the IBS microbiome is characterized by reduced functional redundancy. Differences in microbial substrate preferences are also linked to bowel functions. Focusing on taxa that drive SCFA profiles and stool form may be a rational strategy for identifying relevant microbial targets in IBS and other DGBI.
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Ju X, Jiang Z, Ma J, Yang D. Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis. Nutrients 2024; 16:1727. [PMID: 38892659 PMCID: PMC11174707 DOI: 10.3390/nu16111727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 05/20/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
CONTEXT Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting. OBJECTIVE Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases. DATA SOURCES A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction. DATA ANALYSIS It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion. CONCLUSIONS The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.
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Affiliation(s)
| | | | | | - Dong Yang
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China; (X.J.); (Z.J.); (J.M.)
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10
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Meng X, Shi M, Guo G, Xing J, Liu Z, Song F, Liu S. In-depth investigation of the therapeutic effect of Tribulus terrestris L. on type 2 diabetes based on intestinal microbiota and feces metabolomics. JOURNAL OF ETHNOPHARMACOLOGY 2024; 325:117815. [PMID: 38309487 DOI: 10.1016/j.jep.2024.117815] [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: 09/22/2023] [Revised: 01/16/2024] [Accepted: 01/21/2024] [Indexed: 02/05/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The fruit of Tribulus terrestris L. (TT) is extensively documented in the Tibetan medical literature 'Si Bu Yi Dian', has been used to treat diabetes mellitus for more than a thousand years. However, the underlying mechanisms and comprehensive effects of TT on diabetes have yet to be investigated. AIM OF THE STUDY The aim of the study was to systemically elucidate the potential mechanisms of TT in treating diabetes mellitus, and further investigate the therapeutic effects of the water extract, small molecular components and saccharides from TT. MATERIALS AND METHODS Fecal metabolomics was employed to draw the metabolic profile based on UHPLC-Q-TOF-MS/MS. The V3-V4 hypervariable regions of the bacteria 16S rRNA gene were amplified to explore the structural changes of the intestinal microbiome after TT intervention and to analyze the differential microbiota. The microbial metabolites SCFAs were determined by GC-MS, and the BAs and tryptophan metabolites were quantified by UPLC-TQ-MS. Spearman correlation analysis was carried out to comprehensively investigate the relationship among the endogenous metabolites profile, intestinal microbiota and their metabolites. RESULTS TT exhibited remarkably therapeutic effect on T2DM rats, as evidenced by improved glucolipid metabolism and intestinal barrier integrity, ameliorated inflammation and remission in insulin resistance. A total of 24 endogenous biomarkers were screened through fecal metabolomics studies, which were mainly related to tryptophan metabolism, fatty acid metabolism, bile acid metabolism, steroid hormone biosynthesis and arachidonic acid metabolism. Investigations on microbiomics revealed that TT significantly modulated 18 differential bacterial genera and reversed the disordered gut microbial in diabetes rats. Moreover, TT notably altered the content of gut microbiota metabolites, both in serum and fecal samples. Significant correlation among microbial community, metabolites and T2DM-related indicators was revealed. CONCLUSIONS The multiple components of TT regulate the metabolic homeostasis of the organism and the balance of intestinal microbiota and its metabolites, which might mediate the anti-diabetic capacity of TT.
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Affiliation(s)
- Xin Meng
- State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026, Hefei, China.
| | - Minjie Shi
- State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026, Hefei, China.
| | - Guangpeng Guo
- State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026, Hefei, China.
| | - Junpeng Xing
- State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China.
| | - Zhiqiang Liu
- State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China.
| | - Fengrui Song
- State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026, Hefei, China.
| | - Shu Liu
- State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026, Hefei, China.
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11
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Sellge G. Bakterielle Fehlbesiedlung des Dünndarms. AKTUELLE ERNÄHRUNGSMEDIZIN 2024; 49:156-172. [DOI: 10.1055/a-2258-8105] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
SIBO (Small Intestinal Bacterial Overgrowth) ist durch eine bakterielle
Überwucherung oder Fehlbesiedlung des Dünndarms in Kombination mit intestinalen
Symptomen definiert. Intestinale Stase, Hypochlorhydrie, Immundefizienz, Alter
u.a. sind auslösende Faktoren. Die Therapie beinhaltet die Behandlung der
auslösenden Grunderkrankung, den Ausgleich einer Mangelernährung, den Einsatz
von Antibiotika und Probiotika sowie diätetische Maßnahmen.
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12
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Thwaites PA, Yao CK, Halmos EP, Muir JG, Burgell RE, Berean KJ, Kalantar‐zadeh K, Gibson PR. Review article: Current status and future directions of ingestible electronic devices in gastroenterology. Aliment Pharmacol Ther 2024; 59:459-474. [PMID: 38168738 PMCID: PMC10952964 DOI: 10.1111/apt.17844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/15/2023] [Accepted: 12/13/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Advances in microelectronics have greatly expanded the capabilities and clinical potential of ingestible electronic devices. AIM To provide an overview of the structure and potential impact of ingestible devices in development that are relevant to the gastrointestinal tract. METHODS We performed a detailed literature search to inform this narrative review. RESULTS Technical success of ingestible electronic devices relies on the ability to miniaturise the microelectronic circuits, sensors and components for interventional functions while being sufficiently powered to fulfil the intended function. These devices offer the advantages of being convenient and minimally invasive, with real-time assessment often possible and with minimal interference to normal physiology. Safety has not been a limitation, but defining and controlling device location in the gastrointestinal tract remains challenging. The success of capsule endoscopy has buoyed enthusiasm for the concepts, but few ingestible devices have reached clinical practice to date, partly due to the novelty of the information they provide and also due to the challenges of adding this novel technology to established clinical paradigms. Nonetheless, with ongoing technological advancement and as understanding of their potential impact emerges, acceptance of such technology will grow. These devices have the capacity to provide unique insight into gastrointestinal physiology and pathophysiology. Interventional functions, such as sampling of tissue or luminal contents and delivery of therapies, may further enhance their ability to sharpen gastroenterological diagnoses, monitoring and treatment. CONCLUSIONS The development of miniaturised ingestible microelectronic-based devices offers exciting prospects for enhancing gastroenterological research and the delivery of personalised, point-of-care medicine.
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Affiliation(s)
- Phoebe A. Thwaites
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Chu K. Yao
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Emma P. Halmos
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Jane G. Muir
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Rebecca E. Burgell
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Kyle J. Berean
- Atmo BiosciencesMelbourneVictoriaAustralia
- School of Engineering, RMIT UniversityMelbourneVictoriaAustralia
| | - Kourosh Kalantar‐zadeh
- Faculty of Engineering, School of Chemical and Biomolecular EngineeringThe University of SydneyCamperdownNew South WalesAustralia
| | - Peter R. Gibson
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
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13
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Bertin L, Zanconato M, Crepaldi M, Marasco G, Cremon C, Barbara G, Barberio B, Zingone F, Savarino EV. The Role of the FODMAP Diet in IBS. Nutrients 2024; 16:370. [PMID: 38337655 PMCID: PMC10857121 DOI: 10.3390/nu16030370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 01/23/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024] Open
Abstract
The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the low FODMAP diet works is still not completely understood. These mechanisms encompass not only traditionally known factors such as luminal distension induced by gas and water but also recent evidence on the role of FOMAPs in the modulation of visceral hypersensitivity, increases in intestinal permeability, the induction of microbiota changes, and the production of short-chain fatty acids (SCFAs), as well as metabolomics and alterations in motility. Although most of the supporting evidence is of low quality, recent trials have confirmed its effectiveness, even though the majority of the evidence pertains only to the restriction phase and its effectiveness in relieving abdominal bloating and pain. This review examines potential pathophysiological mechanisms and provides an overview of the existing evidence on the effectiveness of the low FODMAP diet across various IBS subtypes. Key considerations for its use include the challenges and disadvantages associated with its practical implementation, including the need for professional guidance, variations in individual responses, concerns related to microbiota, nutritional deficiencies, the development of constipation, the necessity of excluding an eating disorder before commencing the diet, and the scarcity of long-term data. Despite its recognized efficacy in symptom management, acknowledging these limitations becomes imperative for a nuanced comprehension of the role of a low FODMAP diet in managing IBS. By investigating its potential mechanisms and evidence across IBS subtypes and addressing emerging modulations alongside limitations, this review aims to serve as a valuable resource for healthcare practitioners, researchers, and patients navigating the intricate landscape of IBS.
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Affiliation(s)
- Luisa Bertin
- Department of Surgery, Oncology, Gastroenterology, University of Padua, 35121 Padua, Italy; (L.B.); (M.Z.); (M.C.); (B.B.); (F.Z.)
- Gastroenterology Unit, Azienda Ospedale-Università Padova, 35128 Padua, Italy
| | - Miriana Zanconato
- Department of Surgery, Oncology, Gastroenterology, University of Padua, 35121 Padua, Italy; (L.B.); (M.Z.); (M.C.); (B.B.); (F.Z.)
- Gastroenterology Unit, Azienda Ospedale-Università Padova, 35128 Padua, Italy
| | - Martina Crepaldi
- Department of Surgery, Oncology, Gastroenterology, University of Padua, 35121 Padua, Italy; (L.B.); (M.Z.); (M.C.); (B.B.); (F.Z.)
- Gastroenterology Unit, Azienda Ospedale-Università Padova, 35128 Padua, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (G.M.); (C.C.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (G.M.); (C.C.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy; (G.M.); (C.C.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Brigida Barberio
- Department of Surgery, Oncology, Gastroenterology, University of Padua, 35121 Padua, Italy; (L.B.); (M.Z.); (M.C.); (B.B.); (F.Z.)
- Gastroenterology Unit, Azienda Ospedale-Università Padova, 35128 Padua, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology, Gastroenterology, University of Padua, 35121 Padua, Italy; (L.B.); (M.Z.); (M.C.); (B.B.); (F.Z.)
- Gastroenterology Unit, Azienda Ospedale-Università Padova, 35128 Padua, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology, Gastroenterology, University of Padua, 35121 Padua, Italy; (L.B.); (M.Z.); (M.C.); (B.B.); (F.Z.)
- Gastroenterology Unit, Azienda Ospedale-Università Padova, 35128 Padua, Italy
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14
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Zhou J, Wei H, Zhou A, Xiao X, Xie X, Tang B, Lin H, Tang L, Meng R, Yuan X, Zhang J, Huang C, Huang B, Liao X, Zhong T, He S, Gu S, Yang S. The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study. J Transl Med 2024; 22:98. [PMID: 38263117 PMCID: PMC10807057 DOI: 10.1186/s12967-024-04898-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 01/14/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).
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Affiliation(s)
- Jianyun Zhou
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Haoqi Wei
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - An Zhou
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Xu Xiao
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Xia Xie
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Bo Tang
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Hui Lin
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Li Tang
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Ruiping Meng
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Xiaoying Yuan
- Department of Gastroenterology, The Ninth People's Hospital of Chongqing, No. 69 Jialing Village, Beibei District, Chongqing, China, 400700
| | - Jing Zhang
- Department of Gastroenterology, Chongqing University Jiangjin Hospital, No.725, Jiangzhou Avenue, Jiangjin District, Chongqing, China, 402260
| | - Cheng Huang
- Department of Gastroenterology, Chonggang General Hospital, No. 1 Dayan Sancun, Dadukou District, Chongqing, China, 400000
| | - Baobao Huang
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Xiping Liao
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Tingting Zhong
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037
| | - Suyu He
- Department of Gastroenterology, Suining Central Hospital, 22 Youfang Street, Chuanshan District, Suining, China, 629000.
| | - Sai Gu
- Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University Jinshan Campus, 50 Jinyu Dadao, Liangjiang New District, Chongqing, China, 401112.
| | - Shiming Yang
- Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
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15
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Gargari G, Mantegazza G, Taverniti V, Gardana C, Valenza A, Rossignoli F, Barbaro MR, Marasco G, Cremon C, Barbara G, Guglielmetti S. Fecal short-chain fatty acids in non-constipated irritable bowel syndrome: a potential clinically relevant stratification factor based on catabotyping analysis. Gut Microbes 2023; 15:2274128. [PMID: 37910479 PMCID: PMC10773536 DOI: 10.1080/19490976.2023.2274128] [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: 07/12/2023] [Accepted: 10/18/2023] [Indexed: 11/03/2023] Open
Abstract
The gut microbiota is believed to be a critical factor in the pathogenesis of IBS, and its metabolic byproducts, such as short-chain fatty acids (SCFAs), are known to influence gut function and host health. Despite this, the precise role of SCFAs in IBS remains a topic of debate. In this study, we examined the bacterial community structure by 16S rRNA gene profiling and SCFA levels by UPLC-MS/MS in fecal samples from healthy controls (HC; n = 100) and non-constipated patients (IBS-D and IBS-M; NC-IBS; n = 240) enrolled in 19 hospitals in Italy. Our findings suggest a significant difference between the fecal microbiomes of NC-IBS patients and HC subjects, with HC exhibiting higher intra-sample biodiversity. Furthermore, we were able to classify non-constipated patients into two distinct subgroups based on their fecal SCFA levels (fecal catabotype "high" and "low"), each characterized by unique taxonomic bacterial signatures. Our results suggest that the fecal catabotype with higher SCFA levels may represent a distinct clinical phenotype of IBS that could have implications for its diagnosis and treatment. This study provides a new perspective on the intricate relationship between the gut microbiome and bowel symptoms in IBS, underscoring the importance of personalized strategies for its management.
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Affiliation(s)
- Giorgio Gargari
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Giacomo Mantegazza
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Valentina Taverniti
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Claudio Gardana
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Alice Valenza
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Federico Rossignoli
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Maria Raffaella Barbaro
- Dipartimento di Scienze Mediche e Chirurgiche, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Marasco
- Dipartimento di Scienze Mediche e Chirurgiche, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Cesare Cremon
- Dipartimento di Scienze Mediche e Chirurgiche, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Barbara
- Dipartimento di Scienze Mediche e Chirurgiche, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Simone Guglielmetti
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
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16
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Liu XY, Wu SD. Fecal microbiota transplantation for treatment of irritable bowel syndrome: Current advances and future perspectives. Shijie Huaren Xiaohua Zazhi 2023; 31:922-932. [DOI: 10.11569/wcjd.v31.i22.922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/27/2023] [Accepted: 11/19/2023] [Indexed: 11/28/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a kind of functional gastroin-testinal disorder, characterized by recurrent abdominal pain and altered bowel habits. IBS adversely affects the quality of life of patients for the lack of effective treatment. The etiology of IBS remains poorly known. Previous studies suggested a possible role of gut dysbiosis in IBS pathogenesis. Fecal microbiota transplantation (FMT), which aims to reverse the gut dysbiosis, is a promising strategy in IBS management. In this review, we summarize the role of the gut microbiota in IBS pathogenesis from different aspects. We also review recent studies on efficacy evaluation of FMT in IBS. Besides, we discuss factors affecting the efficacy of FMT, hoping to provide a reference for future IBS treatment strategies targeting the gut microbiota.
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Affiliation(s)
- Xin-Yi Liu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Sheng-Di Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
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Nikolaki MD, Kasti AN, Katsas K, Petsis K, Lambrinou S, Patsalidou V, Stamatopoulou S, Karlatira K, Kapolos J, Papadimitriou K, Triantafyllou K. The Low-FODMAP Diet, IBS, and BCFAs: Exploring the Positive, Negative, and Less Desirable Aspects-A Literature Review. Microorganisms 2023; 11:2387. [PMID: 37894045 PMCID: PMC10609264 DOI: 10.3390/microorganisms11102387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/14/2023] [Accepted: 09/22/2023] [Indexed: 10/29/2023] Open
Abstract
The literature about the association of branched short-chain fatty acids (BCFAs) and irritable bowel syndrome (IBS) is limited. BCFAs, the bacterial products of the catabolism of branched-chain amino acids, are proposed as markers for colonic protein fermentation. IBS is a gastrointestinal disorder characterized by low-grade inflammation and intestinal dysbiosis. The low-FODMAP diet (LFD) has increasingly been applied as first-line therapy for managing IBS symptoms, although it decreases the production of short-chain fatty acids (SCFA), well known for their anti-inflammatory action. In parallel, high protein consumption increases BCFAs. Protein fermentation alters the colonic microbiome through nitrogenous metabolites production, known for their detrimental effects on the intestinal barrier promoting inflammation. Purpose: This review aims to explore the role of BCFAs on gut inflammation in patients with IBS and the impact of LFD in BCFAs production. Methods: A literature search was carried out using a combination of terms in scientific databases. Results: The included studies have contradictory findings about how BCFAs affect the intestinal health of IBS patients. Conclusions: Although evidence suggests that BCFAs may play a protective role in gut inflammation, other metabolites of protein fermentation are associated with gut inflammation. Further research is needed in order to clarify how diet protein composition and, consequently, the BCFAs are implicated in IBS pathogenesis or in symptoms management with LFD+.
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Affiliation(s)
- Maroulla D. Nikolaki
- Department of Nutrition and Dietetics, ATTIKON University General Hospital, 12462 Athens, Greece; (M.D.N.); (A.N.K.); (K.K.); (K.P.); (V.P.); (S.S.); (K.K.)
- Department of Nutrition and Dietetics Sciences, Hellenic Mediterranean University, 72300 Crete, Greece
| | - Arezina N. Kasti
- Department of Nutrition and Dietetics, ATTIKON University General Hospital, 12462 Athens, Greece; (M.D.N.); (A.N.K.); (K.K.); (K.P.); (V.P.); (S.S.); (K.K.)
| | - Konstantinos Katsas
- Department of Nutrition and Dietetics, ATTIKON University General Hospital, 12462 Athens, Greece; (M.D.N.); (A.N.K.); (K.K.); (K.P.); (V.P.); (S.S.); (K.K.)
- Institute of Preventive Medicine Environmental and Occupational Health Prolepsis, 15125 Athens, Greece
| | - Konstantinos Petsis
- Department of Nutrition and Dietetics, ATTIKON University General Hospital, 12462 Athens, Greece; (M.D.N.); (A.N.K.); (K.K.); (K.P.); (V.P.); (S.S.); (K.K.)
| | - Sophia Lambrinou
- Department of Clinical Nutrition & Dietetics, General Hospital of Karpathos “Aghios Ioannis o Karpathios”, 85700 Karpathos, Greece;
| | - Vasiliki Patsalidou
- Department of Nutrition and Dietetics, ATTIKON University General Hospital, 12462 Athens, Greece; (M.D.N.); (A.N.K.); (K.K.); (K.P.); (V.P.); (S.S.); (K.K.)
| | - Sophia Stamatopoulou
- Department of Nutrition and Dietetics, ATTIKON University General Hospital, 12462 Athens, Greece; (M.D.N.); (A.N.K.); (K.K.); (K.P.); (V.P.); (S.S.); (K.K.)
| | - Katerina Karlatira
- Department of Nutrition and Dietetics, ATTIKON University General Hospital, 12462 Athens, Greece; (M.D.N.); (A.N.K.); (K.K.); (K.P.); (V.P.); (S.S.); (K.K.)
| | - John Kapolos
- Department of Food Science and Technology, University of Peloponnese, 24100 Kalamata, Greece;
| | - Konstantinos Papadimitriou
- Laboratory of Food Quality Control and Hygiene, Department of Food Science and Human Nutrition, Agricultural University of Athens, 11855 Athens, Greece;
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, 2nd Department of Internal Propaedeutic Medicine, Medical School, National and Kapodistrian University of Athens, ATTIKON University General Hospital, 12462 Athens, Greece
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18
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So D, Yao CK, Gill PA, Thwaites PA, Ardalan ZS, McSweeney CS, Denman SE, Chrimes AF, Muir JG, Berean KJ, Kalantar‐Zadeh K, Gibson PR. Detection of changes in regional colonic fermentation in response to supplementing a low FODMAP diet with dietary fibres by hydrogen concentrations, but not by luminal pH. Aliment Pharmacol Ther 2023; 58:417-428. [PMID: 37386938 PMCID: PMC10946934 DOI: 10.1111/apt.17629] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/04/2023] [Accepted: 06/15/2023] [Indexed: 07/01/2023]
Abstract
BACKGROUND Carbohydrate fermentation plays a pivotal role in maintaining colonic health with excessive proximal and deficient distal fermentation being detrimental. AIMS To utilise telemetric gas- and pH-sensing capsule technologies for defining patterns of regional fermentation following dietary manipulations, alongside conventional techniques of measuring fermentation. METHODS In a double-blind crossover trial, 20 patients with irritable bowel syndrome were fed low FODMAP diets that included no extra fibre (total fibre content 24 g/day), or additional poorly fermented fibre, alone (33 g/day) or with fermentable fibre (45 g/day) for 2 weeks. Plasma and faecal biochemistry, luminal profiles defined by tandem gas- and pH-sensing capsules, and faecal microbiota were assessed. RESULTS Plasma short-chain fatty acid (SCFA) concentrations (μmol/L) were median (IQR) 121 (100-222) with fibre combination compared with 66 (44-120) with poorly fermented fibre alone (p = 0.028) and 74 (55-125) control (p = 0.069), but no differences in faecal content were observed. Luminal hydrogen concentrations (%), but not pH, were higher in distal colon (mean 4.9 [95% CI: 2.2-7.5]) with fibre combination compared with 1.8 (0.8-2.8) with poorly fermented fibre alone (p = 0.003) and 1.9 (0.7-3.1) control (p = 0.003). Relative abundances of saccharolytic fermentative bacteria were generally higher in association with supplementation with the fibre combination. CONCLUSIONS A modest increase in fermentable plus poorly fermented fibres had minor effects on faecal measures of fermentation, despite increases in plasma SCFA and abundance of fermentative bacteria, but the gas-sensing capsule, not pH-sensing capsule, detected the anticipated propagation of fermentation distally in the colon. The gas-sensing capsule technology provides unique insights into localisation of colonic fermentation. TRIAL REGISTRATION ACTRN12619000691145.
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Affiliation(s)
- Daniel So
- Department of GastroenterologyCentral Clinical School, Monash University and Alfred HealthMelbourneAustralia
| | - Chu K. Yao
- Department of GastroenterologyCentral Clinical School, Monash University and Alfred HealthMelbourneAustralia
| | - Paul A. Gill
- Department of GastroenterologyCentral Clinical School, Monash University and Alfred HealthMelbourneAustralia
| | - Phoebe A. Thwaites
- Department of GastroenterologyCentral Clinical School, Monash University and Alfred HealthMelbourneAustralia
| | - Zaid S. Ardalan
- Department of GastroenterologyCentral Clinical School, Monash University and Alfred HealthMelbourneAustralia
| | - Chris S. McSweeney
- Agriculture and FoodCommonwealth Scientific and Industrial Research OrganisationSt. LuciaAustralia
| | - Stuart E. Denman
- Agriculture and FoodCommonwealth Scientific and Industrial Research OrganisationSt. LuciaAustralia
| | - Adam F. Chrimes
- Atmo BiosciencesMelbourneAustralia
- School of Engineering, RMIT UniversityMelbourneAustralia
| | - Jane G. Muir
- Department of GastroenterologyCentral Clinical School, Monash University and Alfred HealthMelbourneAustralia
| | - Kyle J. Berean
- Atmo BiosciencesMelbourneAustralia
- School of Engineering, RMIT UniversityMelbourneAustralia
| | - Kourosh Kalantar‐Zadeh
- School of Chemical Engineering, University of New South WalesSydneyAustralia
- Faculty of EngineeringSchool of Chemical and Biomolecular Engineering, The University of SydneySydneyAustralia
| | - Peter R. Gibson
- Department of GastroenterologyCentral Clinical School, Monash University and Alfred HealthMelbourneAustralia
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19
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Kovaleva A, Poluektova E, Maslennikov R, Zolnikova O, Shifrin O, Kudryavtseva A, Krasnov G, Fedorova M, Karchevskaya A, Ivashkin V. Structure and Metabolic Activity of the Gut Microbiota in Diarrhea-Predominant Irritable Bowel Syndrome Combined with Functional Dyspepsia. GASTROINTESTINAL DISORDERS 2023; 5:296-309. [DOI: 10.3390/gidisord5030024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/26/2024] Open
Abstract
Gut dysbiosis presents in many digestive diseases. The aim of this study is to investigate the composition of the gut microbiota and its metabolic activity in patients with diarrhea-predominant irritable bowel syndrome combined with functional dyspepsia (I + D). This study included 60 patients with I + D and 20 healthy controls. Gut microbiota composition was studied using 16S rRNA gene sequencing. The short-chain fatty acids (SCFAs) spectrum was determined via gas–liquid chromatography. Patients with I + D had an increase in the abundance of Holdemanella, Erysipelotrichaceae, Erysipelotrichales, Prevotellaceae, Agathobacter, Slackia, Lactococcus, Pseudomonadaceae, Stenotrophomonas, Xanthomonadaceae, Rhizobiaceae, Erysipelatoclostridiaceae, Lachnospiraceae, and other taxa in addition to a decrease in the abundance of Frisingicoccus, Ralstonia, Burkholderiaceae, Hungatella, Eisenbergiella, Parabacteroides, Peptostreptococcaceae, Merdibacter, Bilophila, Rikenellaceae, Tannerellaceae, Bacteroidaceae, and Flavonifractor in comparison to controls. Patients with I + D showed significantly higher total SCFA content in feces; increased absolute content of acetic acid, propionic acid, butyric acid, and isoacids; and a significant negative shift in the anaerobic index. The relative levels of the main SCFAs and isoacids in the patient group did not differ significantly from those in the control group. The fecal acetate and isoacid levels correlated with the severity of diarrhea. The fecal butyrate level correlated with the severity of flatulence.
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Affiliation(s)
- Aleksandra Kovaleva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119991, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119991, Russia
- Consultative and Diagnostic Center No. 2 of the Moscow Health Department, Moscow 107564, Russia
| | - Oxana Zolnikova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia
| | - Oleg Shifrin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia
| | - Anna Kudryavtseva
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - George Krasnov
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - Maria Fedorova
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - Anna Karchevskaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia
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20
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Maqoud F, Tricarico D, Mallamaci R, Orlando A, Russo F. The Role of Ion Channels in Functional Gastrointestinal Disorders (FGID): Evidence of Channelopathies and Potential Avenues for Future Research and Therapeutic Targets. Int J Mol Sci 2023; 24:11074. [PMID: 37446251 DOI: 10.3390/ijms241311074] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
Several gastrointestinal (GI) tract abnormalities, including visceral hypersensitivity, motility, and intestinal permeability alterations, have been implicated in functional GI disorders (FGIDs). Ion channels play a crucial role in all the functions mentioned above. Hormones and natural molecules modulate these channels and represent targets of drugs and bacterial toxins. Mutations and abnormal functional expression of ion channel subunits can lead to diseases called channelopathies. These channelopathies in gastroenterology are gaining a strong interest, and the evidence of co-relationships is increasing. In this review, we describe the correlation status between channelopathies and FGIDs. Different findings are available. Among others, mutations in the ABCC7/CFTR gene have been described as a cause of constipation and diarrhea. Mutations of the SCN5A gene are instead associated with irritable bowel syndrome. In contrast, mutations of the TRPV1 and TRPA genes of the transient receptor potential (TRP) superfamily manifest hypersensitivity and visceral pain in sensory nerves. Recently, mice and humans affected by Cantu syndrome (CS), which is associated with the mutations of the KCNJ8 and ABCC9 genes encoding for the Kir6.1 and SUR2 subunits, showed dysfunction of contractility throughout the intestine and death in the mice after the weaning on solid food. The discovery of a correlation between channelopathies and FIGD opens new avenues for discovering new direct drug targets for specific channelopathies, leading to significant implications for diagnosing and treating functional GI diseases.
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Affiliation(s)
- Fatima Maqoud
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Castellana Grotte, 70013 Bari, Italy
| | - Domenico Tricarico
- Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, 70125 Bari, Italy
| | - Rosanna Mallamaci
- Department of Biosciences, Biotechnologies and Environment University of Bari Aldo Moro, 70125 Bari, Italy
| | - Antonella Orlando
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Castellana Grotte, 70013 Bari, Italy
| | - Francesco Russo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Castellana Grotte, 70013 Bari, Italy
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21
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Mao B, Xiang Q, Tang X, Zhang Q, Liu X, Zhao J, Cui S, Zhang H. Lactobacillus reuteri CCFM1175 and Lactobacillus paracasei CCFM1176 Could Prevent Capsaicin-Induced Ileal and Colonic Injuries. Probiotics Antimicrob Proteins 2023:10.1007/s12602-023-10106-1. [PMID: 37314694 DOI: 10.1007/s12602-023-10106-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/05/2023] [Indexed: 06/15/2023]
Abstract
Capsaicin (CAP) is usually reported to have many biological activities. However, a large intake of CAP may cause heartburn, gastrointestinal pain, and diarrhea. In this study, mice were gavaged with nine lactic acid bacteria (LAB) strains for two weeks, in which the mice were treated with CAP at the second week and lasted for one week. We tried to identify potential probiotics that could prevent CAP-induced intestinal injury and investigate the mechanisms. The modulation of transient receptor potential vanilloid 1 (TRPV1), levels of short-chain fatty acids (SCFAs), and the composition of gut microbiota were analyzed. The results showed that Lactobacillus reuteri CCFM1175 and Lactobacillus paracasei CCFM1176 effectively attenuated CAP-induced injuries to the ileum and colon, including relieving the damage to colonic crypt structures, increasing the number of goblet cells, decreasing levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), increasing levels of anti-inflammatory factors (IL-10), and reducing levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in serum and colon tissue. Further analysis showed that L. reuteri CCFM1175 increased the relative abundance of Ruminococcaceae UCG_014 and Akkermansia. L. paracasei CCFM1176 downregulated the expression of TRPV1 in the ileal and colonic tissues and promoted the relative abundance of Ruminococcaceae UCG_014 and Lachnospiraceae UCG_006. These results indicate that L. reuteri CCFM1175 and L. paracasei CCFM1176 could prevent CAP-induced intestinal injury and be used as probiotics to improve the gastrointestinal health.
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Affiliation(s)
- Bingyong Mao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Qunran Xiang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Xin Tang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Qiuxiang Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Xiaoming Liu
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Shumao Cui
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China.
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.
| | - Hao Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
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22
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Chen X, Hu C, Yan C, Tao E, Zhu Z, Shu X, Guo R, Jiang M. Maternal separation leads to dynamic changes of visceral hypersensitivity and fecal metabolomics from childhood to adulthood. Sci Rep 2023; 13:7670. [PMID: 37169847 PMCID: PMC10175246 DOI: 10.1038/s41598-023-34792-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/08/2023] [Indexed: 05/13/2023] Open
Abstract
We assessed dynamic changes in visceral hypersensitivity and fecal metabolomics through a mouse model of irritable bowel syndrome (IBS) from childhood to adulthood. A mouse model of IBS was constructed with maternal separation (MS) in early life. Male mice aged 25, 40, and 70 days were used. Visceral sensitivity was assessed by recording the reaction between the abdominal withdrawal reflex and colorectal distension. Metabolomics was identified and quantified by liquid chromatography-tandem mass spectrometry. The visceral sensitivity of the MS group was significantly higher than that of the non-separation (NS) group in the three age groups. The top four fecal differential metabolites in the different age groups were lipids, lipid molecules, organic heterocyclic compounds, organic acids and derivatives, and benzenoids. Five identical differential metabolites were detected in the feces and ileal contents of the MS and NS groups at different ages, namely, benzamide, taurine, acetyl-L-carnitine, indole, and ethylbenzene. Taurine and hypotaurine metabolism were the most relevant pathways at P25, whereas histidine metabolism was the most relevant pathway at P40 and P70. Visceral hypersensitivity in the MS group lasted from childhood to adulthood. The different metabolites and metabolic pathways detected in MS groups of different ages provide a theoretical basis for IBS pathogenesis.
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Affiliation(s)
- Xiaolong Chen
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
- Department of Pediatrics, The First People's Hospital of Jiashan, Jiashan, 314100, China
| | - Chenmin Hu
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Chenxi Yan
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Enfu Tao
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Zhenya Zhu
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Xiaoli Shu
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Rui Guo
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Mizu Jiang
- Pediatric Endoscopy Center and Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China.
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China.
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23
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Zhang VRY, Ramachandran GK, Loo EXL, Soh AYS, Yong WP, Siah KTH. Volatile organic compounds as potential biomarkers of irritable bowel syndrome: A systematic review. Neurogastroenterol Motil 2023:e14536. [PMID: 36780514 DOI: 10.1111/nmo.14536] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 01/02/2023] [Accepted: 01/11/2023] [Indexed: 02/15/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease characterized by intermittent abdominal pain with altered bowel habits. Due to the condition's chronicity, patients suffer from poor quality of life, while the healthcare burden continues to grow. There is currently no reliable biomarker for the diagnosis of IBS, and the current approach depends on ruling-out organic diseases such as inflammatory bowel disease (IBD) and colorectal cancer by markers of inflammation like fecal calprotectin and C-reactive protein, or invasive procedures like a colonoscopy. Volatile organic compounds (VOCs) are growing in popularity as a biomarker due to its accuracy and ease of use. PURPOSE This systematic review of Medline and Cochrane's databases aimed to identify VOCs in the diagnosis of IBS. 57% of the studies proved that VOCs could identify IBS patients from healthy controls with AUC ranging from 0.83 to 0.99. Studies that distinguished IBS from IBD patients had slightly higher AUC of 0.87-0.98. Combining VOC into panels allowed the creation of discriminative algorithms. Though current research is limited by areas of heterogeneity in VOC sampling and small sample sizes, our review shows that VOC analysis has the potential to be a noninvasive point-of-care test that differentiates IBS from other organic gastrointestinal diseases.
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Affiliation(s)
| | | | - Evelyn Xiu Ling Loo
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Singapore.,Department of Paediatrics and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Alex Yu Sen Soh
- Division of Gastroenterology & Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
| | - Wei Peng Yong
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.,Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore
| | - Kewin Tien Ho Siah
- Division of Gastroenterology & Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
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24
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Liu J, Ma X, Zhuo Y, Xu S, Hua L, Li J, Feng B, Fang Z, Jiang X, Che L, Zhu Z, Lin Y, Wu D. The Effects of Bacillus subtilis QST713 and β-mannanase on growth performance, intestinal barrier function, and the gut microbiota in weaned piglets. J Anim Sci 2023; 101:skad257. [PMID: 37583344 PMCID: PMC10449409 DOI: 10.1093/jas/skad257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 08/08/2023] [Indexed: 08/17/2023] Open
Abstract
We investigated the effects of different Bacillus subtilis QST713 doses and a B. subtilis QST713 and β-mannanase mix on growth performance, intestinal barrier function, and gut microbiota in weaned piglets. In total, 320 healthy piglets were randomly assigned to four groups: 1) control group (basal diet), 2) BS100 group (basal diet plus 100 mg/kg B. subtilis QST713), 3) BS200 group (basal diet plus 200 mg/kg B. subtilis QST713), and 4) a BS100XT group (basal diet plus 100 mg/kg B. subtilis QST713 and 150 mg/kg β-mannanase). The study duration was 42 d. We showed that feed intake in weaned piglets on days 1 to 21 was increased in group BS100 (P < 0.05), and that the feed conversion ratio in group BS100XT animals decreased throughout the study (P < 0.05). In terms of microbial counts, the BS100XT group showed reduced Escherichia coli and Clostridium perfringens numbers on day 21 (P < 0.05). Moreover, no significant α-diversity differences were observed across all groups during the study (P > 0.05). However, principal coordinates analysis indicated clear separations in bacterial community structures across groups (analysis of similarities: P < 0.05) on days 21 and 42. Additionally, E-cadherin, occludin, and zonula occludens-1 (ZO-1) expression in piglet feces increased (P < 0.05) by adding B. subtilis QST713 and β-mannanase to diets. Notably, this addition decreased short-chain fatty acid concentrations. In conclusion, B. subtilis QST713 addition or combined B. subtilis QST713 plus β-mannanase effectively improved growth performance, intestinal barrier function, and microbial balance in weaned piglets.
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Affiliation(s)
- Junchen Liu
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Xiangyuan Ma
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Yong Zhuo
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Shengyu Xu
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Lun Hua
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Jian Li
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Bin Feng
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Zhengfeng Fang
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Xuemei Jiang
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Lianqiang Che
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Zeyuan Zhu
- Elanco Animal Health, Mutiara Damansara, Selangor, Malaysia
| | - Yan Lin
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - De Wu
- Institute of Animal Nutrition, Key Laboratory for Animal Disease-Resistance Nutrition of China, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
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Waseem MR, Shin A, Siwiec R, James-Stevenson T, Bohm M, Rogers N, Wo J, Waseem L, Gupta A, Jarrett M, Kadariya J, Xu H. Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome. Clin Transl Gastroenterol 2023; 14:e00541. [PMID: 36227781 PMCID: PMC9875959 DOI: 10.14309/ctg.0000000000000541] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 09/23/2022] [Accepted: 10/03/2022] [Indexed: 01/31/2023] Open
Abstract
INTRODUCTION Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. METHODS We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. RESULTS Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [-0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). DISCUSSION Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.
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Affiliation(s)
- Mohammed Rayyan Waseem
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Robert Siwiec
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Toyia James-Stevenson
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Matthew Bohm
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Nicholas Rogers
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - John Wo
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Lina Waseem
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Anita Gupta
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Megan Jarrett
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Jhalka Kadariya
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Huiping Xu
- Department of Biostatistics and Health Data Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Procházková N, Falony G, Dragsted LO, Licht TR, Raes J, Roager HM. Advancing human gut microbiota research by considering gut transit time. Gut 2023; 72:180-191. [PMID: 36171079 PMCID: PMC9763197 DOI: 10.1136/gutjnl-2022-328166] [Citation(s) in RCA: 96] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 09/10/2022] [Indexed: 02/04/2023]
Abstract
Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet-microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.
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Affiliation(s)
- Nicola Procházková
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Gwen Falony
- Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium
- Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
| | - Lars Ove Dragsted
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
| | - Tine Rask Licht
- National Food Institute, Technical University, Kgs. Lyngby, Denmark
| | - Jeroen Raes
- Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium
- Center for Microbiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
| | - Henrik M Roager
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
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Zhao C, Jiang Y, Yin H, Jin Z, Yuan J, Shang H, Song H. Hericium caput-medusae (Bull.: Fr.) Pers. Fermentation concentrate polysaccharide ameliorate diarrhea in DSS-induced early colitis by modulating ion channel. J Funct Foods 2023. [DOI: 10.1016/j.jff.2022.105390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Chen YH, Chen SCJ, Wang JW, Liu CS, Wu JY, Wu DC, Su YC. Exhaled Hydrogen after Lactulose Hydrogen Breath Test in Patient with Duodenal Ulcer Disease-A Pilot Study for Helicobacter-pylori-Associated Gastroduodenal Disease. LIFE (BASEL, SWITZERLAND) 2022; 13:life13010045. [PMID: 36675994 PMCID: PMC9863152 DOI: 10.3390/life13010045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/07/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022]
Abstract
OBJECTIVES The precipitating mechanism(s) from the inactive to the active stage of duodenal ulcer disease (DU) is unclear. It has been shown that hydrogen gas from colonic fermentation provides an important energy source for Helicobacter pylori (Hp) colonization. The lactulose hydrogen breath test (LHBT) is a useful tool to assess the small intestinal and/or colon fermentation. This study examines the association(s) between the status of gastroduodenal disease and the result of a lactulose hydrogen breath test (LHBT). MATERIALS AND METHODS We enrolled Hp-positive active duodenal ulcer (aDU) patients, inactive DU (iDU) patients and patients with a positive Hp infection without structural gastroduodenal lesion, i.e., simple gastritis (SG Hp+). The patients with simple gastritis without Hp infection (SG Hp-) served as controls. Histological examinations of the gastric mucosa and lactulose hydrogen breath test (LHBT) were performed. RESULTS SG Hp+ patients tend to have advanced gastritis (pangastritis or corpus-predominant gastritis) compared with SG Hp- patients (7/29 vs. 0/14, p = 0.08). More iDU patients had advanced gastritis than either the SG Hp+ (7/9 vs. 7/29, p = 0.006) or aDU patients (7/9 vs. 6/24, p = 0.013). In comparison with the aDU patients, the iDU patients were also older (52.1 ± 12.6 vs. 42.2 ± 11.9 years, p = 0.02) and had a lower mean area under the curve value of the LHBT(AUC) (209.1 ± 86.0 vs. 421.9 ± 70.9, p = 0.023). CONCLUSION aDU patients with a positive Hp infection have a lower grade of gastric mucosa damage than iDU patients and tend to have a higher level of exhaled hydrogen after LHBT.
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Affiliation(s)
- Yi-Hsun Chen
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
| | - Sharon Chia-Ju Chen
- Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
| | - Jiunn-Wei Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
| | - Chiang-Shin Liu
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Jeng-Yih Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
| | - Yu-Chung Su
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80756, Taiwan
- Correspondence: ; Tel.: +886-7-3121101-7451
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Cheng F, Fan Z, Lin C, Zhu Y, He H, Dai N, Du L. Effect of altered gut microbiota on visceral hypersensitivity of postinfectious irritable bowel syndrome mice. Eur J Gastroenterol Hepatol 2022; 34:1220-1230. [PMID: 36165068 DOI: 10.1097/meg.0000000000002441] [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] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized with visceral hypersensitivity. Previous studies indicated gut microbiota alteration associated short-chain fatty acids (SCFAs) dysregulation is associated with IBS development. The aim of the study is to explore the potential role of microbiota dysbiosis mediated visceral hypersensitivity in postinfectious-IBS (PI-IBS) mouse model. METHODS Four-week-old NIH mice were randomly allocated into four groups: control mice, PI-IBS mice, PI-IBS mice co-housing with normal mice, and PI-IBS mice were administrated with a cocktail of antibiotics. Trichinella spiralis infection established PI-IBS mouse model. Microbiota in cecal contents and feces were analyzed by 16S rDNA sequencing. SCFAs were detected by gas chromatography. 5-hydroxytryptamine (5-HT) was evaluated by ELISA, and N-methyl-D-aspartate receptors (NMDARs) were examined by western blot. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distention. RESULTS Increased SCFAs were observed in cecal contents and feces in PI-IBS mice accompanied with higher 5-HT and NMDAR subunits expressions in ileum and colon. Visceral hypersensitivity was observed in PI-IBS mice compared to control mice. When administrated with antibiotics cocktails and co-housing with normal mice, PI-IBS mice showed decreased SCFAs, 5-HT, NMDAR subunits expressions, and improved visceral hypersensitivity. CONCLUSION Gut microbiota alteration induced increased SCFAs, 5-HT and NMDAR subunits expressions were associated with visceral hypersensitivity in PI-IBS mice. The critical role of gut microbiota in improving visceral hypersensitivity was further identified by treatment of antibiotics cocktail and co-housing.
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Affiliation(s)
- Fangli Cheng
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
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30
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McHarg AS, Leach S. The role of the gut microbiome in paediatric irritable bowel syndrome. AIMS Microbiol 2022; 8:454-469. [PMID: 36694592 PMCID: PMC9834077 DOI: 10.3934/microbiol.2022030] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/10/2022] [Accepted: 11/14/2022] [Indexed: 11/23/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common and disabling condition in children. The pathophysiology of IBS is thought to be multifactorial but remains incompletely understood. There is growing evidence implicating the gut microbiome in IBS. Intestinal dysbiosis has been demonstrated in paediatric IBS cohorts; however, no uniform or consistent pattern has been identified. The exact mechanisms by which this dysbiosis contributes to IBS symptoms remain unknown. Available evidence suggests the imbalance produces a functional dysbiosis, with altered production of gases and metabolites that interact with the intestinal wall to cause symptoms, and enrichment or depletion of certain metabolic pathways. Additional hypothesised mechanisms include increased intestinal permeability, visceral hypersensitivity and altered gastrointestinal motility; however, these remain speculative in paediatric patients, with studies limited to animal models and adult populations. Interaction between dietary components and intestinal microbiota, particularly with fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), has drawn increasing attention. FODMAPs have been found to trigger and worsen IBS symptoms. This is thought to be related to products of their fermentation by a dysbiotic microbial population, although this remains to be proven. A low-FODMAP diet has shown promising success in ameliorating symptoms in some but not all patients. There remains much to be discovered about the role of the dysbiotic microbiome in paediatric IBS.
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Affiliation(s)
- Alexandra S McHarg
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia,Westfield Research Laboratories, Sydney Children's Hospital, Randwick, NSW, Australia,* Correspondence:
| | - Steven Leach
- School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia,Westfield Research Laboratories, Sydney Children's Hospital, Randwick, NSW, Australia
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31
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Xie QQ, Wang JF, Zhang YF, Xu DH, Zhou B, Li TH, Li ZP. Glucose substrate in the hydrogen breath test for gut microbiota determination: A recommended noninvasive test. World J Clin Cases 2022; 10:9536-9538. [PMID: 36159421 PMCID: PMC9477675 DOI: 10.12998/wjcc.v10.i26.9536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/06/2022] [Accepted: 08/06/2022] [Indexed: 02/05/2023] Open
Abstract
Intestinal dysbiosis and small intestinal bacterial overgrowth (SIBO) are common in patients with liver cirrhosis. Existing studies have not explored the association between gut dysbiosis and SIBO. We propose some suggestions for the authors’ experimental methods and concepts, and we hope these suggestions can be adopted. The hydrogen breath test is worthy of recommendation due to its high accuracy and convenient operation. We suggest changing the substrate of the hydrogen breath test from lactulose to glucose to improve the accuracy of each parameter. SIBO is a small subset of gut dysbiosis, and we propose clarifying the concept of both. SIBO may be caused by liver cirrhosis or one of the pathogeneses of gastrointestinal diseases. Therefore, interference from other gastrointestinal diseases should be excluded from this study.
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Affiliation(s)
- Qi-Qi Xie
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Jia-Feng Wang
- Town Hospital of Gaodu, Mengyin County, Linyi 276200, Shandong Province, China
| | - Yang-Fen Zhang
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Dong-Hui Xu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Bo Zhou
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Ting-Hui Li
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Zhi-Peng Li
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
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Bushyhead D, Quigley EMM. Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management. Gastroenterology 2022; 163:593-607. [PMID: 35398346 DOI: 10.1053/j.gastro.2022.04.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 03/28/2022] [Accepted: 04/03/2022] [Indexed: 12/19/2022]
Abstract
The concept of small intestinal bacterial overgrowth (SIBO) arose in the context of maldigestion and malabsorption among patients with obvious risk factors that permitted the small bowel to be colonized by potentially injurious colonic microbiota. Such colonization resulted in clinical signs, symptoms, and laboratory abnormalities that were explicable within a coherent pathophysiological framework. Coincident with advances in medical science, diagnostic testing evolved from small bowel culture to breath tests and on to next-generation, culture-independent microbial analytics. The advent and ready availability of breath tests generated a dramatic expansion in both the rate of diagnosis of SIBO and the range of associated gastrointestinal and nongastrointestinal clinical scenarios. However, issues with the specificity of these same breath tests have clouded their interpretation and aroused some skepticism regarding the role of SIBO in this expanded clinical repertoire. Furthermore, the pathophysiological plausibility that underpins SIBO as a cause of maldigestion/malabsorption is lacking in regard to its purported role in irritable bowel syndrome, for example. One hopes that the application of an ever-expanding armamentarium of modern molecular microbiology to the human small intestinal microbiome in both health and disease will ultimately resolve this impasse and provide an objective basis for the diagnosis of SIBO.
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Affiliation(s)
- Daniel Bushyhead
- Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.
| | - Eamonn M M Quigley
- Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas
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Abstract
INTRODUCTION Patients with irritable bowel syndrome (IBS) frequently resort to natural products, or request doctors to prescribe them, to relieve their symptoms, due to the poor efficacy and tolerability of several traditional drugs. Products containing fiber are among the most used and their clinical efficacy is discussed here based on the most recent scientific evidence. AREAS COVERED A literature search was carried out to identify the most significant publications in order to deal with the topics of the general characteristics of fibers and the scientific evidence underlying their therapeutic use, the properties of ispaghula husk and the mechanisms by which this product carries out its therapeutic actions. EXPERT OPINION The most recent clinical guidelines on the management of IBS consider ispaghula husk, a product containing soluble fiber, as a reasonable first line therapy for IBS patients with symptoms. In contrast, products containing insoluble fibers, particularly wheat bran, do not appear to be useful in treating IBS symptoms. The clinical data on the use of prebiotics in IBS are still inconclusive. However, low daily amounts of fructo-oligosaccharides or β-galacto-oligosaccharides (also known as trans-galacto-oligosaccharides) may be effective in improving IBS symptoms; further trials are needed to definitively establish their clinical usefulness.
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Affiliation(s)
- Diego Currò
- Dipartimento Di Sicurezza E Bioetica, Sezione Di Farmacologia, Università Cattolica Del Sacro Cuore - Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
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O'Riordan KJ, Collins MK, Moloney GM, Knox EG, Aburto MR, Fülling C, Morley SJ, Clarke G, Schellekens H, Cryan JF. Short chain fatty acids: Microbial metabolites for gut-brain axis signalling. Mol Cell Endocrinol 2022; 546:111572. [PMID: 35066114 DOI: 10.1016/j.mce.2022.111572] [Citation(s) in RCA: 198] [Impact Index Per Article: 66.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 01/07/2022] [Accepted: 01/11/2022] [Indexed: 02/08/2023]
Abstract
The role of the intestinal microbiota as a regulator of gut-brain axis signalling has risen to prominence in recent years. Understanding the relationship between the gut microbiota, the metabolites it produces, and the brain will be critical for the subsequent development of new therapeutic approaches, including the identification of novel psychobiotics. A key focus in this regard have been the short-chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fibre, which include butyrate, acetate, and propionate. Ongoing research is focused on the entry of SCFAs into systemic circulation from the gut lumen, their migration to cerebral circulation and across the blood brain barrier, and their potential to exert acute and chronic effects on brain structure and function. This review aims to discuss our current mechanistic understanding of the direct and indirect influence that SCFAs have on brain function, behaviour and physiology, which will inform future microbiota-targeted interventions for brain disorders.
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Affiliation(s)
| | - Michael K Collins
- APC Microbiome Ireland, University College Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Ireland
| | - Gerard M Moloney
- APC Microbiome Ireland, University College Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Ireland
| | - Emily G Knox
- APC Microbiome Ireland, University College Cork, Ireland; School of Pharmacy, University College Cork, Ireland
| | - María R Aburto
- APC Microbiome Ireland, University College Cork, Ireland
| | | | - Shane J Morley
- APC Microbiome Ireland, University College Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Harriët Schellekens
- APC Microbiome Ireland, University College Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Ireland.
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Staudacher HM, Rossi M, Kaminski T, Dimidi E, Ralph FSE, Wilson B, Martin LD, Louis P, Lomer MCE, Irving PM, Whelan K. Long-term personalized low FODMAP diet improves symptoms and maintains luminal Bifidobacteria abundance in irritable bowel syndrome. Neurogastroenterol Motil 2022; 34:e14241. [PMID: 34431172 DOI: 10.1111/nmo.14241] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 06/03/2021] [Accepted: 07/17/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Short-term trials demonstrate the low FODMAP diet improves symptoms of irritable bowel syndrome (IBS) but impacts nutrient intake and the gastrointestinal microbiota. The aim of this study was to investigate clinical symptoms, nutrient intake, and microbiota of patients with IBS 12 months after starting a low FODMAP diet. METHODS Participants enrolled in a previous short-term clinical trial and who had been through structured FODMAP restriction, reintroduction, and personalization were invited to participate in a follow-up study at one time point at 12 months. Gastrointestinal symptoms, stool output, dietary intake, and quality of life were recorded. Stool samples were collected and analyzed for microbiota (qPCR) and short-chain fatty acids (SCFA). Data were compared with baseline (prior to any intervention in the original clinical trial) using non-parametric statistics. KEY RESULTS Eighteen participants were included in the study. Adequate relief of symptoms occurred in 5/18 (28%) at baseline and increased to 12/18 (67%) following long-term personalized low FODMAP diet (p = 0.039). There was a reduction in IBS-SSS total score between baseline (median 227, IQR 99) and long term (154, 89; p < 0.001). Bifidobacteria abundance was not different between baseline (median 9.29 log10 rRNA genes/g, IQR 1.45) and long term (9.20 log10 rRNA genes/g, 1.41; p = 0.766, q = 0.906); however, there were lower concentrations of total SCFA, acetate, propionate, and butyrate. CONCLUSIONS In this long-term analysis, two thirds of patients reported adequate relief of symptoms after 12 months of personalized low FODMAP diet that did not result in differences from baseline in Bifidobacteria. FODMAP reintroduction and personalization may normalize some of the effects of short-term FODMAP restriction.
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Affiliation(s)
- Heidi M Staudacher
- Department of Nutritional Sciences, King's College London, London, UK.,Food & Mood Centre, Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Victoria, Australia
| | - Megan Rossi
- Department of Nutritional Sciences, King's College London, London, UK
| | - Thomas Kaminski
- Department of Nutritional Sciences, King's College London, London, UK
| | - Eirini Dimidi
- Department of Nutritional Sciences, King's College London, London, UK
| | - Frances S E Ralph
- Department of Nutritional Sciences, King's College London, London, UK
| | - Bridgette Wilson
- Department of Nutritional Sciences, King's College London, London, UK
| | - Lee D Martin
- Department of Nutritional Sciences, King's College London, London, UK
| | - Petra Louis
- Gut Health Group, The Rowett Institute, University of Aberdeen, Aberdeen, UK
| | - Miranda C E Lomer
- Department of Nutritional Sciences, King's College London, London, UK.,Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Peter M Irving
- Department of Nutritional Sciences, King's College London, London, UK.,Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Kevin Whelan
- Department of Nutritional Sciences, King's College London, London, UK
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Calderon G, Patel C, Camilleri M, James-Stevenson T, Bohm M, Siwiec R, Rogers N, Wo J, Lockett C, Gupta A, Xu H, Shin A. Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome. J Clin Gastroenterol 2022; 56:234-242. [PMID: 33780215 PMCID: PMC8435047 DOI: 10.1097/mcg.0000000000001521] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/29/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND GOALS Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). STUDY In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. RESULTS Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. CONCLUSIONS Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.
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Affiliation(s)
- Gerardo Calderon
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Chirag Patel
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Toyia James-Stevenson
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Matthew Bohm
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Robert Siwiec
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Nicholas Rogers
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - John Wo
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Carolyn Lockett
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Anita Gupta
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Huiping Xu
- Department of Biostatistics; Indiana University School of Medicine, Indianapolis, IN
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
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Mishra V, Bose A, Kiran S, Banerjee S, Shah IA, Chaukimath P, Reshi MM, Srinivas S, Barman A, Visweswariah SS. Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C. J Exp Med 2021; 218:212653. [PMID: 34546338 PMCID: PMC8480670 DOI: 10.1084/jem.20210479] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 07/30/2021] [Accepted: 09/01/2021] [Indexed: 12/13/2022] Open
Abstract
Activating mutations in receptor guanylyl cyclase C (GC-C), the target of gastrointestinal peptide hormones guanylin and uroguanylin, and bacterial heat-stable enterotoxins cause early-onset diarrhea and chronic inflammatory bowel disease (IBD). GC-C regulates ion and fluid secretion in the gut via cGMP production and activation of cGMP-dependent protein kinase II. We characterize a novel mouse model harboring an activating mutation in Gucy2c equivalent to that seen in an affected Norwegian family. Mutant mice demonstrated elevated intestinal cGMP levels and enhanced fecal water and sodium content. Basal and linaclotide-mediated small intestinal transit was higher in mutant mice, and they were more susceptible to DSS-induced colitis. Fecal microbiome and gene expression analyses of colonic tissue revealed dysbiosis, up-regulation of IFN-stimulated genes, and misregulation of genes associated with human IBD and animal models of colitis. This novel mouse model thus provides molecular insights into the multiple roles of intestinal epithelial cell cGMP, which culminate in dysbiosis and the induction of inflammation in the gut.
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Affiliation(s)
- Vishwas Mishra
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Avipsa Bose
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Shashi Kiran
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Sanghita Banerjee
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Idrees A Shah
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Pooja Chaukimath
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Mudasir M Reshi
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Swarna Srinivas
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Anaxee Barman
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
| | - Sandhya S Visweswariah
- Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India
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Burns GL, Hoedt EC, Walker MM, Talley NJ, Keely S. Physiological mechanisms of unexplained (functional) gastrointestinal disorders. J Physiol 2021; 599:5141-5161. [PMID: 34705270 DOI: 10.1113/jp281620] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/20/2021] [Indexed: 12/13/2022] Open
Abstract
Functional gastrointestinal disorders (FGIDs) encompass a range of complex conditions with similar clinical characteristics and no overt pathology. Recent recognition of sub-clinical pathologies in FGIDs, in conjunction with physiological and biochemical abnormalities including increased intestinal permeability, microbial profile alterations, differences in metabolites and extra-intestinal manifestations of disease, call into question the designation of these conditions as 'functional'. This is despite significant heterogeneity in both symptom profile and specifics of reported physiological abnormalities hampering efforts to determine defined mechanisms that drive onset and chronicity of symptoms. Instead, the literature demonstrates these conditions are disorders of homeostatic imbalance, with disruptions in both host and microbial function and metabolism. This imbalance is also associated with extraintestinal abnormalities including psychological comorbidities and fatigue that may be a consequence of gastrointestinal disruption. Given the exploitation of such abnormalities will be crucial for improved therapeutic selection, an enhanced understanding of the relationship between alterations in function of the gastrointestinal tract and the response of the immune system is of interest in identifying mechanisms that drive FGID onset and chronicity. Considerations for future research should include the role of sex hormones in regulating physiological functions and treatment responses in patients, as well as the importance of high-level phenotyping of clinical, immune, microbial and physiological parameters in study cohorts. There is opportunity to examine the functional contribution of the microbiota and associated metabolites as a source of mechanistic insight and targets for therapeutic modulation.
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Affiliation(s)
- Grace L Burns
- School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre for Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia.,New Lambton Heights, Hunter Medical Research Institute, Newcastle, NSW, Australia
| | - Emily C Hoedt
- NHMRC Centre for Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia.,New Lambton Heights, Hunter Medical Research Institute, Newcastle, NSW, Australia.,School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia
| | - Marjorie M Walker
- NHMRC Centre for Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia.,New Lambton Heights, Hunter Medical Research Institute, Newcastle, NSW, Australia.,School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia
| | - Nicholas J Talley
- NHMRC Centre for Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia.,New Lambton Heights, Hunter Medical Research Institute, Newcastle, NSW, Australia.,School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia
| | - Simon Keely
- School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre for Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia.,New Lambton Heights, Hunter Medical Research Institute, Newcastle, NSW, Australia
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Xiao L, Liu Q, Luo M, Xiong L. Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome. Front Cell Infect Microbiol 2021; 11:729346. [PMID: 34631603 PMCID: PMC8495119 DOI: 10.3389/fcimb.2021.729346] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/25/2021] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is associated with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiology remains poorly understood. Gut microbiota and its metabolites are proposed as possible etiological factors of IBS. The aim of our study was to investigate specific types of microbiota-derived metabolites, especially bile acids, short-chain fatty acids, vitamins, amino acids, serotonin and hypoxanthine, which are all implicated in the pathogenesis of IBS. Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established. Thus, we provide an overview of gut microbiota and their metabolites on the different subtypes of IBS (constipation-predominant IBS-C, diarrhea-predominant IBS-D) and present controversial views regarding the role of microbiota in IBS.
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Affiliation(s)
- Lin Xiao
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qin Liu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mei Luo
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lishou Xiong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Hang L, Zhou Y, Meng YY, Feng Y, Wang YS, Yuan JY. Progress in understanding of relationship between short chain fatty acids and irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2021; 29:1102-1109. [DOI: 10.11569/wcjd.v29.i19.1102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a functional intestinal disease whose pathogenesis has not yet been fully defined. The main clinical manifestations of IBS are irregular abdominal pain, abdominal distension, and changes in stool character and defecation habits. As one of the pathogeneses of IBS, intestinal flora imbalance plays an important role in the development of IBS. The vast majorities of short chain fatty acids (SCFAs) are produced through the interaction of intestinal flora with host diet in the colon. As one of the main metabolites of intestinal flora, SCFAs have the effects of intestinal barrier protection, immune regulation, anti-inflammation, and regulation of visceral sensitivity in the intestine. In recent years, with the increasing attention to SCFAs, studies on the relationship between SCFAs and IBS are emerging. This review summarizes the progress in the understanding of the relationship between SCFAs and IBS in recent five years.
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Affiliation(s)
- Lu Hang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yan Zhou
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yang-Yang Meng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Ya Feng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yin-Shu Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jian-Ye Yuan
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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Clinical assessment and cytokines level in constipation-predominant irritable bowel syndrome participants treated with Lactobacillus-containing cultured milk drink. Acta Gastroenterol Belg 2021; 84:585-591. [PMID: 34965040 DOI: 10.51821/84.4.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND Gut dysbiosis is linked with the pathophysiology of irritable bowel syndrome (IBS). Manipulation of intestinal microbiota using cultured milk drinks may stimulate the immune system, hence providing beneficial support in IBS treatment. This study aimed to investigate the effects of cultured milk drink on clinical symptoms, intestinal transit time (ITT), fecal pH and cytokines in constipation-predominant IBS (IBS-C) as compared to non-IBS participants. METHODS Each recruited participant was given three bottles of 125 ml cultured milk drink containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 consumed daily for 30 days. At pre- and post-30-day consumption, fecal pH, ITT, clinical symptoms, IL-6, IL-8 and TNF-α levels were assessed. Seventy-seven IBS-C and 88 non-IBS were enrolled. RESULTS Post-consumption, 97.4% of IBS-C experienced improvements in constipation-related symptoms supported by the significant reduction of ITT and decreased fecal pH (p<0.05). All pro-inflammatory cytokines were significantly lower in post as compared to pre-consumption of cultured milk drinks in IBS-C (p<0.05). There was significant reduction in the IL-8 and TNF-α levels in post- as compared to pre-consumption for the non-IBS (p<0.05). CONCLUSION Cultured milk drink taken daily improved clinical symptoms and reduced cytokines, hence should be considered as an adjunctive treatment in IBS-C individuals.
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Yao CK, Burgell RE, Taylor KM, Ward MG, Friedman AB, Barrett JS, Muir JG, Gibson PR. Effects of fiber intake on intestinal pH, transit, and predicted oral mesalamine delivery in patients with ulcerative colitis. J Gastroenterol Hepatol 2021; 36:1580-1589. [PMID: 33091174 DOI: 10.1111/jgh.15311] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 09/15/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Limited data are available on the effects of fermentable fiber in altering intestinal pH and transit to predict efficacy-based delivery profiles of pH-dependent mesalamine coatings in ulcerative colitis (UC). This study aimed to examine regional pH and transit after acute changes in fermentable fiber intake in quiescent UC patients and their effects on drug release systems. METHODS In a randomized, double-blind study, 18 patients with quiescent UC and 10 healthy controls were supplied meals high (13 g) or low (≤ 2 g) in fermentable fiber and subsequently ingested a wireless pH-motility capsule. After a ≥ 3-day washout, they crossed over to the other diet. Measurements of intestinal pH and transit were used to predict drug release for the various pH-dependent coatings. RESULTS Increasing fermentable fiber intake lowered overall (median 6.2 [6.1-6.7] vs low: 6.9 [range or interquartile range: 6.4-7.4]; P = 0.01) and distal pH (7.8 [7.3-8.1] vs 8.2 [8.0-8.5]; P = 0.04) in controls. In UC patients, only cecal pH was decreased (high: 5.1 [4.8-5.5] vs low: 5.5 [5.3-5.7]; P < 0.01). Colonic transit in the UC cohort varied widely after a low-fiber intake but tended to normalize after the high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients, with a multi-matrix delayed release system having the highest likelihood of patients (20-40%) with incomplete dissolution, and predominant small intestinal dissolution predicted for Eudragit L (94% patients) and S (44-69%). CONCLUSIONS Patients with quiescent UC have abnormalities in intestinal pH and transit in response to acute changes in fermentable fiber intake. These have potentially detrimental effects on predicted luminal release patterns of pH-dependent 5-aminosalicylic acid release systems.
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Affiliation(s)
- Chu K Yao
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Rebecca E Burgell
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Kirstin M Taylor
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Mark G Ward
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Antony B Friedman
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Jacqueline S Barrett
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Jane G Muir
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
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Abstract
The term "small intestinal bacterial overgrowth" (SIBO) has been used to refer to a disorder resulting from the colonization of the small bowel by an increased number of microorganisms or by the presence of bacteria that are not usual constituents of this part of the gastrointestinal tract. Clinical presentations, often in patients with certain risk factors, can range from a full-blown malabsorption syndrome to such "functional" complaints as bloating and flatulence. SIBO is diagnosed by either culture of a small bowel aspirate or one of several breath tests. Treatment of SIBO entails risk factor modification, correction of nutritional deficiencies, and oral antibiotics.
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Affiliation(s)
- Daniel Bushyhead
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, 6550 Fannin Street Suite 1201, Houston, TX 77030, USA.
| | - Eamonn M Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, 6550 Fannin Street Suite 1201, Houston, TX 77030, USA
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Zhang Z, Lin T, Meng Y, Hu M, Shu L, Jiang H, Gao R, Ma J, Wang C, Zhou X. FOS/GOS attenuates high-fat diet induced bone loss via reversing microbiota dysbiosis, high intestinal permeability and systemic inflammation in mice. Metabolism 2021; 119:154767. [PMID: 33753088 DOI: 10.1016/j.metabol.2021.154767] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 03/03/2021] [Accepted: 03/17/2021] [Indexed: 01/26/2023]
Abstract
BACKGROUND Obesity and osteoporosis frequently coexist, and might have a causal relationship. Gut microbiota, associated with both lipid and bone metabolism, plays an important role in the pathogenesis of excessive fat accumulation and bone loss. The improvement of intestinal flora by prebiotics was a promising strategy for ameliorating obesity-related bone loss. METHODS Obesity model was established by feeding mice with high fat diet (HFD) for 16 weeks. Fructooligosaccharides (FOS) and/or galactooligosaccharides (GOS) were daily gavaged to mice. Osteoblastic, adipocytic, and osteoclastic differentiation was performed on primary cells isolated from experimental mice. The composition of gut flora was evaluated by 16s rDNA sequencing. Expression of intestinal junction proteins was assessed by qPCR and immunohistochemistry. Cytokine levels were measured by qPCR. RESULTS Long-term HFD caused decreased bone mass in mice, which was associated with decreased osteogenesis, increased osteoclastogenesis, and excessive adipogenesis. FOS/GOS treatment significantly alleviated HFD-induced bone loss and reversed the imbalanced differentiation of osteoblasts, adipocytes, and osteoclasts. In addition, our study showed that FOS/GOS administration ameliorated microbiota dysbiosis (manifested as enhanced Firmicutes:Bacteriodetes ratio and reduced biodiversity), downregulated expression of intestinal junction proteins (including Claudin1, Claudin15, ZO-1, and JAM-A), and increased inflammatory cytokines (including TNFα, IL6, and IL17) in HFD-fed mice. CONCLUSION Long-term HFD led to decreased bone mass, with microbiota dysbiosis, leaky gut, and systemic inflammation. The administration of FOS/GOS could significantly increase biodiversity and SCFA concentrations of intestinal flora in HFD fed mice, then reverse high gut permeability and inflammatory cytokines, in the end protect against HFD induced osteopenia.
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Affiliation(s)
- Zheng Zhang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China; College of basic medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China
| | - Tao Lin
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China
| | - Yichen Meng
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China
| | - Miao Hu
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China; College of basic medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China
| | - Lun Shu
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China; College of basic medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China
| | - Heng Jiang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China
| | - Rui Gao
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China
| | - Jun Ma
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China.
| | - Ce Wang
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China.
| | - Xuhui Zhou
- Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, People's Republic of China.
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Sun QH, Liu ZJ, Zhang L, Wei H, Song LJ, Zhu SW, He MB, Duan LP. Sex-based differences in fecal short-chain fatty acid and gut microbiota in irritable bowel syndrome patients. J Dig Dis 2021; 22:246-255. [PMID: 33822477 PMCID: PMC8252430 DOI: 10.1111/1751-2980.12988] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 03/06/2021] [Accepted: 04/05/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To explore alterations in fecal short-chain fatty acids (SCFA) and gut microbiota in patients with diarrhea-predominant irritable bowel disease (IBS-D) and their relationships with clinical manifestations. METHODS We recruited 162 patients with IBS-D and 66 healthy controls (HC). Their manifestations and psychological status were evaluated using the IBS severity scoring system and the Hospital Anxiety and Depression Scale (HADS). Colorectal visceral sensitivity was evaluated using a barostat. Systemic inflammation was evaluated using plasma cytokine levels. Fecal SCFA were quantified using ultra-performance liquid chromatography-tandem mass spectrometry, and fecal microbiota communities were analyzed using 16S rRNA sequencing. RESULTS More men presented with IBS-D than women in our patient cohort. Patients with IBS-D had more severe manifestations, higher HADS score, and a higher rate of previous infectious enteritis than HC. Notably, female patients had significantly higher HADS scores than male patients. Male patients had significantly higher levels of plasma interleukin (IL)-12, fecal propionate and colorectal visceral sensitivity than male HC, while no differences were observed between female patients and female HC. Fecal acetate, butyrate and valerate correlated with the initial visceral sensory threshold, stressors, and IL-10 and IL-12 levels. The propionate-producing Prevotella 9 genus was significantly increased in male patients and positively correlated with fecal propionate. CONCLUSION Distinct sex-based differences in clinical manifestations, fecal SCFA and microbiota richness are found in Chinese patients with IBS-D, which may be used to diagnose dysbiosis in these patients.
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Affiliation(s)
- Qing Hua Sun
- Department of GastroenterologyPeking University Third HospitalBeijingChina
| | - Zuo Jing Liu
- Department of GastroenterologyPeking University Third HospitalBeijingChina
| | - Lu Zhang
- Department of GastroenterologyPeking University Third HospitalBeijingChina
| | - Hui Wei
- Department of GastroenterologyPeking University Third HospitalBeijingChina
| | - Li Jin Song
- Department of GastroenterologyPeking University Third HospitalBeijingChina
| | - Shi Wei Zhu
- Department of GastroenterologyPeking University Third HospitalBeijingChina
| | - Mei Bo He
- Institute of Systems Biomedicine, School of Basic Medical SciencesPeking UniversityBeijingChina
| | - Li Ping Duan
- Department of GastroenterologyPeking University Third HospitalBeijingChina
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Fredericks E, Theunissen R, Roux S. Short chain fatty acids and monocarboxylate transporters in irritable bowel syndrome. TURKISH JOURNAL OF GASTROENTEROLOGY 2021; 31:840-847. [PMID: 33625995 DOI: 10.5152/tjg.2020.19856] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Gut microbiota ferments indigestible food that rests in the colon to produce short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. Colonic SCFA stimulate the synthesis of serotonin which is central in irritable bowel syndrome (IBS) pathophysiology. Reduced SCFA have been linked to specific IBS symptoms like colonic hyperalgesia and hypersensitivity. SCFA enter the colonocyte mainly via 2 energy-dependent monocarboxylate transporters, MCT1 (SLC16A1) and SMCT1 (SLC5A8). We investigated specific gut microbiota, SCFA concentrations, and monocarboxylate transporter mRNA expression in patients with IBS. MATERIAL AND METHODS A total of 30 IBS patients-15 constipation-predominant (C-IBS) and 15 diarrhoea-predominant (D-IBS)-and 15 healthy controls were recruited. Bacteroidetes and Bifidobacterium species were analyzed using quantitative polymerase chain reaction (qPCR) on stool samples. SCFA concentrations were determined by gas chromatography/mass spectroscopy of stool samples. Monocarboxylate transporter mRNA was quantified by qPCR on colon biopsy specimens. RESULTS Bacteroides was significantly increased in the D-IBS group compared with the C-IBS group and healthy controls. Bifidobacterium was significantly reduced in both IBS groups. SCFA ratios were altered in both IBS groups with a reduction of all 3 measured SCFA in C-IBS and acetic acid in D-IBS. MCT1 and SMCT1 were significantly reduced in C-IBS and D-IBS. CONCLUSION In agreement with findings of previous studies, the microbiota assessed were significantly altered inferring dysbiosis in IBS. SCFA and their ratios were significantly altered in both IBS groups. SCFA transporters, MCT1 and SMCT1 were significantly reduced in both IBS groups, suggesting reduced colonocyte SCFA transfer. SCFA availability and transfer into the colonocytes may be important in IBS pathogenesis and should be prospectively studied.
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Affiliation(s)
- Ernst Fredericks
- Department of Physiology, Nelson Mandela University School of Science, Port Elizabeth, South Africa
| | - Reza Theunissen
- Department of Physiology, Nelson Mandela University School of Science, Port Elizabeth, South Africa
| | - Saartjie Roux
- Department of Physiology, Nelson Mandela University School of Science, Port Elizabeth, South Africa
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Luo M, Zhuang X, Tian Z, Xiong L. Alterations in short-chain fatty acids and serotonin in irritable bowel syndrome: a systematic review and meta-analysis. BMC Gastroenterol 2021; 21:14. [PMID: 33407171 PMCID: PMC7788881 DOI: 10.1186/s12876-020-01577-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 12/09/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Short-chain fatty acids (SCFAs) and serotonin (5-hydroxytryptamine, 5-HT) may be associated with the pathogenesis of irritable bowel syndrome (IBS). There are some reports of alterations in SCFAs and 5-HT in IBS, but their results are inconsistent. We aimed to perform a meta-analysis to assess alterations in SCFAs and 5-HT in IBS patients and their potential role in the abnormal brain-gut-microbiota (BGM) axis. METHODS Case-control studies detecting SCFAs and 5-HT in IBS patients were identified from PubMed, Web of Science, Cochrane Library, and Scopus databases to identify relevant articles up to September 2018. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) of SCFAs and 5-HT were calculated by REVIEW MANAGER 5.3 to evaluate the alterations of 5-HT and SCFAs in IBS. RESULTS Five studies on SCFAs and 5 on 5-HT in IBS patients were included. As compared to healthy controls (HCs), the SMDs of 5-HT in IBS patients was 2.35 (95% CI 0.46-4.24) and the SMDs of total SCFAs, acetic acid, propionic acid, and butyric acid in IBS patients were - 0.01 (95% CI - 0.57-0.55), - 0.04 (95% CI - 0.55-0.47), 0.07 (95% CI - 0.45-0.60), and - 0.00 (95% CI - 0.49-0.49), respectively. CONCLUSIONS There was an increase in 5-HT in blood of IBS patients, indicating the increased 5-HT in blood may be involved in IBS pathogenesis. However, there were no significant differences in SCFAs in feces between IBS patients and HCs. But the study did not differentiate between subgroups of IBS. These findings might provide insight for future studies of the BGM axis in the pathogenesis of IBS. Mei Luo and Xiaojun Zhuang contributed equally to the writing of this article.
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Affiliation(s)
- Mei Luo
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiaojun Zhuang
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Zhenyi Tian
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lishou Xiong
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
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Holvoet T, Joossens M, Vázquez-Castellanos JF, Christiaens E, Heyerick L, Boelens J, Verhasselt B, van Vlierberghe H, De Vos M, Raes J, De Looze D. Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial. Gastroenterology 2021; 160:145-157.e8. [PMID: 32681922 DOI: 10.1053/j.gastro.2020.07.013] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 07/02/2020] [Accepted: 07/08/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial. METHODS Patients with refractory IBS, defined as failure of ≥3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial. RESULTS At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse. CONCLUSIONS In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov, Number: NCT02299973.
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Affiliation(s)
- Tom Holvoet
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium; Faculty of Health Sciences, Ghent University, Ghent, Belgium.
| | - Marie Joossens
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium; VIB, Center for Microbiology, Leuven, Belgium
| | - Jorge F Vázquez-Castellanos
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium; VIB, Center for Microbiology, Leuven, Belgium
| | | | - Lander Heyerick
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Jerina Boelens
- Department of Medical Microbiology, Ghent University Hospital, Ghent, Belgium
| | - Bruno Verhasselt
- Department of Medical Microbiology, Ghent University Hospital, Ghent, Belgium
| | | | - Martine De Vos
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Jeroen Raes
- KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Leuven, Belgium; VIB, Center for Microbiology, Leuven, Belgium
| | - Danny De Looze
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium; Faculty of Health Sciences, Ghent University, Ghent, Belgium
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Shin SY, Hussain Z, Lee YJ, Park H. An altered composition of fecal microbiota, organic acids, and the effect of probiotics in the guinea pig model of postoperative ileus. Neurogastroenterol Motil 2021; 33:e13966. [PMID: 32815235 DOI: 10.1111/nmo.13966] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 06/15/2020] [Accepted: 07/21/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The aim of this study is to investigate the altered composition of fecal microbiota, organic acids, and the effect of probiotics in the guinea pig model of the postoperative ileus (POI). METHODS A laparotomy with cecal manipulation was performed to induce POI in guinea pigs. Fecal pellets were collected before the operation (the baseline) and 1, 3, and 5 days after the operation. The extracted fecal DNA was amplified and sequenced using the Illumina MiSeq sequencing system. The same POI procedures were performed after oral pretreatment of the probiotics for 7 days before operation. The effect of the probiotics on the selected taxa and fecal acetate were evaluated, as were the butyrate levels. The colonic transit was assessed by measurement of the fecal pellet output. KEY RESULTS The communities of the baseline and POI groups indicated significantly distinct composition. The genera Bifidobacterium and Lactobacillus were more abundant in the baseline group compared with the POI groups, and Bacteroides and Blautia were more abundant in the POI groups. Decreased abundances of the species Bifidobacterium bifidum and Bifidobacterium longum after the POI procedure were significantly increased in the probiotics group. The decreased fecal butyrate level after the POI procedure was significantly increased, and colonic transit was significantly improved in the probiotics group. CONCLUSIONS AND INFERENCES POI induces gut bacterial dysbiosis. Moreover, pretreatment of probiotics before operation restores the beneficial bacterial species, butyrate production, and bowel movement. The modulation of gut microbiota may help the treatment and prevention of POI.
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Affiliation(s)
- Seung Yong Shin
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Zahid Hussain
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Ju Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyojin Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Liu J, Chey WD, Haller E, Eswaran S. Low-FODMAP Diet for Irritable Bowel Syndrome: What We Know and What We Have Yet to Learn. Annu Rev Med 2020; 71:303-314. [PMID: 31986083 DOI: 10.1146/annurev-med-050218-013625] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Irritable bowel syndrome (IBS) is the most prevalent of gastrointestinal (GI) conditions, affecting millions of people worldwide. Given that most IBS patients associate their GI symptoms with eating food, specific dietary manipulation has become an attractive treatment strategy. A diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) has generated the greatest level of scientific and clinical interest. Overall, 52-86% of patients report significant improvement of their IBS symptoms with elimination of dietary FODMAPs. Patients who experience symptom improvement with FODMAP elimination should undergo a structured reintroduction of foods containing individual FODMAPs to determine sensitivities and allow for personalization of the diet plan. This review discusses the literature surrounding the administration of the low-FODMAP diet and its efficacy in the treatment of IBS.
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Affiliation(s)
- Jerry Liu
- Department of Internal Medicine, University of Texas Southwestern, Dallas, Texas 75390, USA;
| | - William D Chey
- Department of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA; , ,
| | - Emily Haller
- Department of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA; , ,
| | - Shanti Eswaran
- Department of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA; , ,
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