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1
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Dunleavy K, Camilleri M, Raffals L. Altered Bile Acids and Pouch Microbiota Composition in Patients With Chronic Pouchitis. Inflamm Bowel Dis 2025; 31:1184-1187. [PMID: 40073325 DOI: 10.1093/ibd/izaf005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Indexed: 03/14/2025]
Abstract
Lay Summary
This article looks at how changes in bile acids and gut bacteria might contribute to chronic pouchitis, a condition that can develop after surgical removal of the colon and creation of a J-pouch for people with inflammatory bowel disease. The goal is to better understand pouchitis and find treatments to improve patients’ health.
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Affiliation(s)
- Katie Dunleavy
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Michael Camilleri
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Laura Raffals
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
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2
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Bajaj A, Markandey M, Kedia S, Ahuja V. Gut bacteriome in inflammatory bowel disease: An update on recent advances. Indian J Gastroenterol 2024; 43:103-111. [PMID: 38374283 DOI: 10.1007/s12664-024-01541-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 01/25/2024] [Indexed: 02/21/2024]
Abstract
Inflammatory bowel diseases (IBD) are chronic inflammatory gut disorders, majorly classified as ulcerative colitis and Crohn's disease. The complex, multifactorial etiopathogenesis of IBD involves genetic predisposition, environmental cues, aberrant mucosal immune response and a disturbed gut microbiota. Epidemiological trends, studies in gnotobiotic mice models and genome-wide association studies, identifying genes involved in microbial handling, together mount evidence in support of the gut microbiota playing a pivotal role in IBD pathogenesis. Both Crohn's disease and ulcerative colitis are characterized by severe dysbiosis of the gut microbiome, marked by an expansion of detrimental taxa and concomitant depletion of beneficial members. IBD is characterized by reduction in abundances of bacterial genera involved in production of short-chain fatty acids, bio-transformations of bile acids and synthesis of indole-based tryptophan compounds such as Faecalibacterium, Ruminococcus, Coprococcus, Dorea, Parabacteroides, Eubacterium, Oscillibacter and Prevotella and elevation in members of phyla Proteobacteria and Actinobacteria. This imbalance not only results in exaggerated immune signaling towards the microbial antigens, but also results in an altered metabolomic milieu that triggers additional inflammatory cascades. The present review provides insights into the bacterial dysbiosis observed across different intestinal sites and their metabolomic imprints participating in IBD.
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Affiliation(s)
- Aditya Bajaj
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Manasvini Markandey
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India.
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3
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Watson AR, Füssel J, Veseli I, DeLongchamp JZ, Silva M, Trigodet F, Lolans K, Shaiber A, Fogarty E, Runde JM, Quince C, Yu MK, Söylev A, Morrison HG, Lee STM, Kao D, Rubin DT, Jabri B, Louie T, Eren AM. Metabolic independence drives gut microbial colonization and resilience in health and disease. Genome Biol 2023; 24:78. [PMID: 37069665 PMCID: PMC10108530 DOI: 10.1186/s13059-023-02924-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 04/07/2023] [Indexed: 04/19/2023] Open
Abstract
BACKGROUND Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge. RESULTS Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients. CONCLUSIONS These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.
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Affiliation(s)
- Andrea R Watson
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
- Committee On Microbiology, The University of Chicago, Chicago, IL, 60637, USA
| | - Jessika Füssel
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
- Institute for Chemistry and Biology of the Marine Environment, University of Oldenburg, 26129, Oldenburg, Germany
| | - Iva Veseli
- Biophysical Sciences Program, The University of Chicago, Chicago, IL, 60637, USA
| | | | - Marisela Silva
- Department of Medicine, The University of Calgary, Calgary, AB, T2N 1N4, Canada
| | - Florian Trigodet
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Karen Lolans
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Alon Shaiber
- Biophysical Sciences Program, The University of Chicago, Chicago, IL, 60637, USA
| | - Emily Fogarty
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
- Committee On Microbiology, The University of Chicago, Chicago, IL, 60637, USA
| | - Joseph M Runde
- Department of Pediatrics, Lurie Children's Hospital of Chicago, Chicago, IL, 60611, USA
| | - Christopher Quince
- Organisms and Ecosystems, Earlham Institute, Norwich, Norwich, NR4 7UZ, UK
- Gut Microbes and Health, Quadram Institute, Norwich, NR4 7UQ, UK
| | - Michael K Yu
- Toyota Technological Institute at Chicago, Chicago, IL, 60637, USA
| | - Arda Söylev
- Department of Computer Engineering, Konya Food and Agriculture University, Konya, Turkey
| | - Hilary G Morrison
- Marine Biological Laboratory, Josephine Bay Paul Center, Woods Hole, Falmouth, MA, 02543, USA
| | - Sonny T M Lee
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Dina Kao
- Department of Medicine, University of Alberta, Edmonton, AB, T6G 2G3, Canada
| | - David T Rubin
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Bana Jabri
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Thomas Louie
- Department of Medicine, The University of Calgary, Calgary, AB, T2N 1N4, Canada
| | - A Murat Eren
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
- Committee On Microbiology, The University of Chicago, Chicago, IL, 60637, USA.
- Institute for Chemistry and Biology of the Marine Environment, University of Oldenburg, 26129, Oldenburg, Germany.
- Marine Biological Laboratory, Josephine Bay Paul Center, Woods Hole, Falmouth, MA, 02543, USA.
- Helmholtz Institute for Functional Marine Biodiversity, 26129, Oldenburg, Germany.
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Gabbiadini R, Dal Buono A, Correale C, Spinelli A, Repici A, Armuzzi A, Roda G. Ileal Pouch-Anal Anastomosis and Pouchitis: The Role of the Microbiota in the Pathogenesis and Therapy. Nutrients 2022; 14:2610. [PMID: 35807791 PMCID: PMC9268595 DOI: 10.3390/nu14132610] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/15/2022] [Accepted: 06/22/2022] [Indexed: 11/20/2022] Open
Abstract
Inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are life-long disorders characterized by the chronic relapsing inflammation of the gastrointestinal tract with the intermittent need for escalation treatment and, eventually, even surgery. The total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical intervention of choice in subjects affected by ulcerative colitis (UC). Although IPAA provides satisfactory functional outcomes, it can be susceptible to some complications, including pouchitis as the most common. Furthermore, 10-20% of the pouchitis may develop into chronic pouchitis. The etiology of pouchitis is mostly unclear. However, the efficacy of antibiotics in pouchitis suggests that the dysbiosis of the IPAA microbiota plays an important role in its pathogenesis. We aimed to review the role of the microbiota in the pathogenesis and as a target therapy in subjects who develop pouchitis after undergoing the surgical intervention of total proctocolectomy with IPAA reconstruction.
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Affiliation(s)
- Roberto Gabbiadini
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; (R.G.); (A.D.B.); (C.C.); (A.S.); (A.R.); (A.A.)
| | - Arianna Dal Buono
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; (R.G.); (A.D.B.); (C.C.); (A.S.); (A.R.); (A.A.)
| | - Carmen Correale
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; (R.G.); (A.D.B.); (C.C.); (A.S.); (A.R.); (A.A.)
| | - Antonino Spinelli
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; (R.G.); (A.D.B.); (C.C.); (A.S.); (A.R.); (A.A.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Alessandro Repici
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; (R.G.); (A.D.B.); (C.C.); (A.S.); (A.R.); (A.A.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy
| | - Alessandro Armuzzi
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; (R.G.); (A.D.B.); (C.C.); (A.S.); (A.R.); (A.A.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy
| | - Giulia Roda
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; (R.G.); (A.D.B.); (C.C.); (A.S.); (A.R.); (A.A.)
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5
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Gasaly N, de Vos P, Hermoso MA. Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation. Front Immunol 2021; 12:658354. [PMID: 34122415 PMCID: PMC8187770 DOI: 10.3389/fimmu.2021.658354] [Citation(s) in RCA: 276] [Impact Index Per Article: 69.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 04/29/2021] [Indexed: 12/13/2022] Open
Abstract
The diverse and dynamic microbial community of the human gastrointestinal tract plays a vital role in health, with gut microbiota supporting the development and function of the gut immune barrier. Crosstalk between microbiota-gut epithelium and the gut immune system determine the individual health status, and any crosstalk disturbance may lead to chronic intestinal conditions, such as inflammatory bowel diseases (IBD) and celiac disease. Microbiota-derived metabolites are crucial mediators of host-microbial interactions. Some beneficially affect host physiology such as short-chain fatty acids (SCFAs) and secondary bile acids. Also, tryptophan catabolites determine immune responses, such as through binding to the aryl hydrocarbon receptor (AhR). AhR is abundantly present at mucosal surfaces and when activated enhances intestinal epithelial barrier function as well as regulatory immune responses. Exogenous diet-derived indoles (tryptophan) are a major source of endogenous AhR ligand precursors and together with SCFAs and secondary bile acids regulate inflammation by lowering stress in epithelium and gut immunity, and in IBD, AhR expression is downregulated together with tryptophan metabolites. Here, we present an overview of host microbiota-epithelium- gut immunity crosstalk and review how microbial-derived metabolites contribute to host immune homeostasis. Also, we discuss the therapeutic potential of bacterial catabolites for IBD and celiac disease and how essential dietary components such as dietary fibers and bacterial tryptophan catabolites may contribute to intestinal and systemic homeostasis.
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Affiliation(s)
- Naschla Gasaly
- Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Paul de Vos
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, Netherlands
| | - Marcela A Hermoso
- Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.,Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile
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6
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Zhang Q, Tan W, Yang L, Lu M, Dong S, Liu X, Duan X. Multi-Omics Analysis of the Effects of Egg Ovotransferrin on the Gut Environment in Mice: Mucosal Gene Expression, Microbiota Composition, and Intestinal Structural Homeostasis. Mol Nutr Food Res 2020; 64:e1901024. [PMID: 31991508 DOI: 10.1002/mnfr.201901024] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 01/05/2020] [Indexed: 01/29/2023]
Abstract
SCOPE Egg ovotransferrin (OVT) is considered a functional food ingredient for its various bioactivities. The objective of this work is to explore the potential biological activity of OVT on the gut health. METHODS AND RESULTS Both young (3 week old) and adult (8 week old) mouse models are utilized in this research. Each group receives a standard diet containing either OVT (experimental group) or distilled water (control group) for a 14 day period. Transcriptome and 16S rDNA sequencing analyses are applied to characterize the gene expression in colonic epithelial cells and gut microbiota composition. In the young groups, OVT suppresses the genes correlated with lipid metabolism and signal transduction. The regulated genes in the adult groups encompass various biological processes, including lipid metabolism, signal transduction, endocrine system, and others. OVT increases the proportion of some beneficial bacteria significantly, especially Akkermansia, and inhibits some harmful bacteria. Furthermore, OVT affects mucosal morphology positively via increasing the crypt depth. OVT also increases the expression of tight junction protein occludin by 3.0- and 5.2-folds in young and adult groups, respectively. CONCLUSION OVT exhibits some beneficial effects on the gut environment. These positive findings provide new insight into the understanding of OVT as an excellent functional ingredient.
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Affiliation(s)
- Qinjun Zhang
- College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, P. R. China
| | - Wen Tan
- College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, P. R. China
| | - Lu Yang
- College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, P. R. China
| | - Mei Lu
- Department of Food Science and Technology, 249 Food Innovation Center, Lincoln, NE, 68588, USA
| | - Shijian Dong
- Rongda Poultry Farming Co., ltd., Guangde, 242200, Anhui Province, China
| | - Xuebo Liu
- College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, P. R. China
| | - Xiang Duan
- College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, P. R. China
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7
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Shen B. Pathogenesis of Pouchitis. POUCHITIS AND ILEAL POUCH DISORDERS 2019:129-146. [DOI: 10.1016/b978-0-12-809402-0.00011-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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8
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van der Beek CM, Dejong CHC, Troost FJ, Masclee AAM, Lenaerts K. Role of short-chain fatty acids in colonic inflammation, carcinogenesis, and mucosal protection and healing. Nutr Rev 2017; 75:286-305. [PMID: 28402523 DOI: 10.1093/nutrit/nuw067] [Citation(s) in RCA: 243] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Short-chain fatty acids (SCFAs), mainly acetate, propionate, and butyrate, produced by microbial fermentation of undigested food substances are believed to play a beneficial role in human gut health. Short-chain fatty acids influence colonic health through various mechanisms. In vitro and ex vivo studies show that SCFAs have anti-inflammatory and anticarcinogenic effects, play an important role in maintaining metabolic homeostasis in colonocytes, and protect colonocytes from external harm. Animal studies have found substantial positive effects of SCFAs or dietary fiber on colonic disease, but convincing evidence in humans is lacking. Most human intervention trials have been conducted in the context of inflammatory bowel disease. Only a limited number of those trials are of high quality, showing little or no favorable effect of SCFA treatment over placebo. Opportunities for future research include exploring the use of combination therapies with anti-inflammatory drugs, prebiotics, or probiotics; the use of prodrugs in the setting of carcinogenesis; or the direct application of SCFAs to improve mucosal healing after colonic surgery.
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Affiliation(s)
- Christina M van der Beek
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Cornelis H C Dejong
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Freddy J Troost
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Ad A M Masclee
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Kaatje Lenaerts
- C.M. van der Beek, C.H.C. Dejong, F.J. Troost, A.A.M. Masclee, and K. Lenaerts are with Top Institute Food and Nutrition, Wageningen, the Netherlands. C.M. van der Beek, C.H.C. Dejong, and K. Lenaerts are with the Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands. C.H.C. Dejong is with the School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center+, Maastricht, the Netherlands. F.J. Troost and A.A.M. Masclee are with the Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands
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Abstract
A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch. This longitudinal study provides an opportunity to describe shifts in the microbiomes of individual patients who suffer from ulcerative colitis (UC) prior to and following inflammation. Pouchitis serves as a model for UC with a predictable incidence of disease onset and enables prospective longitudinal investigations of UC etiology prior to inflammation. Because of insufficient criteria for predicting which patients will develop UC or pouchitis, the interpretation of cross-sectional study designs suffers from lack of information about the microbiome structure and host gene expression patterns that directly correlate with the onset of disease. Our unique longitudinal study design allows each patient to serve as their own control, providing information about the state of the microbiome and host prior to and during the course of disease. Of significance to the broader community, this study identifies microbial strains that may have genetic elements that trigger the onset of disease in susceptible hosts.
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Schieffer KM, Williams ED, Yochum GS, Koltun WA. Review article: the pathogenesis of pouchitis. Aliment Pharmacol Ther 2016; 44:817-35. [PMID: 27554912 PMCID: PMC5785099 DOI: 10.1111/apt.13780] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 12/03/2015] [Accepted: 08/04/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND A total proctocolectomy followed by ileal pouch-anal anastomosis is a potentially curative surgery for ulcerative colitis or familial adenomatous polyposis. About 5-35% of patients with ulcerative colitis and 0-11% of patients with familial adenomatous polyposis develop subsequent inflammation of the ileal pouch termed pouchitis. AIM To provide a comprehensive analysis of the research studying the possible pathogenesis of pouchitis. The goals were to identify promising areas of investigation, to help focus clinicians, researchers and patients on how to better understand and then potentially manage ileal pouchitis, and to provide avenues for future research investigations. METHODS This review examined manuscripts from 1981 to 2015 that discussed and/or proposed hypotheses with supportive evidence for the potential underlying pathogenic mechanism for pouchitis. RESULTS The pathogenesis of pouchitis is not definitively understood, but various hypotheses have been proposed, including (i) recurrence of ulcerative colitis, (ii) dysbiosis of the ileal pouch microbiota, (iii) deprivation of nutritional short-chain fatty acids, (iv) mucosal ischaemia and oxygen-free radical injury, (v) host genetic susceptibility and (vi) immune dysregulation. However, none of these alone are able to fully explain pouchitis pathogenesis. CONCLUSIONS Pouchitis, similar to inflammatory bowel disease, is a complex disorder that is not caused by any one single factor. More likely, pouchitis occurs through a combination of both dysregulated host inflammatory mechanisms and interaction with luminal microbiota.
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Affiliation(s)
- Kathleen M. Schieffer
- Department of Surgery, Division of Colon and Rectal Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA 17033
| | - Emmanuelle D. Williams
- Department of Medicine, Division of Gastroenterology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA 17033
| | - Gregory S. Yochum
- Department of Surgery, Division of Colon and Rectal Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA 17033,Department of Biochemistry & Molecular Biology, The Pennsylvania State University, College of Medicine, Hershey, PA, USA 17033
| | - Walter A. Koltun
- Department of Surgery, Division of Colon and Rectal Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA 17033
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11
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Putignani L, Del Chierico F, Vernocchi P, Cicala M, Cucchiara S, Dallapiccola B. Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition. Inflamm Bowel Dis 2016; 22:487-504. [PMID: 26588090 DOI: 10.1097/mib.0000000000000602] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastrointestinal disorders, although clinically heterogeneous, share pathogenic mechanisms, including genetic susceptibility, impaired gut barrier function, altered microbiota, and environmental triggers (infections, social and behavioral factors, epigenetic control, and diet). Gut microbiota has been studied for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) in either children or adults, while modifiable gut microbiota features, acting as risk and premorbid factors along the childhood-adulthood transition, have not been thoroughly investigated so far. Indeed, the relationship between variations of the entire host/microbiota/environmental scenario and clinical phenotypes is still not fully understood. In this respect, tracking gut dysbiosis grading may help deciphering host phenotype-genotype associations and microbiota shifts in an integrated top-down omics-based approach within large-scale pediatric and adult case-control cohorts. Large-scale gut microbiota signatures and host inflammation patterns may be integrated with dietary habits, under genetic and epigenetic constraints, providing gut dysbiosis profiles acting as risk predictors of IBD or IBS in preclinical cases. Tracking dysbiosis supports new personalized/stratified IBD and IBS prevention programmes, generating Decision Support System tools. They include (1) high risk or flare-up recurrence -omics-based dysbiosis profiles; (2) microbial and molecular biomarkers of health and disease; (3) -omics-based pipelines for laboratory medicine diagnostics; (4) health apps for self-management of score-based dietary profiles, which can be shared with clinicians for nutritional habit and lifestyle amendment; (5) -omics profiling data warehousing and public repositories for IBD and IBS profile consultation. Dysbiosis-related indexes can represent novel laboratory and clinical medicine tools preventing or postponing the disease, finally interfering with its natural history.
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Affiliation(s)
- Lorenza Putignani
- *Unit of Parasitology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; †Unit of Metagenomics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; ‡Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy; §Department of Pediatrics, Center for Pediatric Inflammatory Bowel Disease, University of Rome "La Sapienza," Rome, Italy; and ‖Scientific Directorate, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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Lichtenstein L, Avni-Biron I, Ben-Bassat O. The current place of probiotics and prebiotics in the treatment of pouchitis. Best Pract Res Clin Gastroenterol 2016; 30:73-80. [PMID: 27048898 DOI: 10.1016/j.bpg.2016.02.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 01/28/2016] [Accepted: 02/02/2016] [Indexed: 01/31/2023]
Abstract
Pouchitis is a common complication in patients undergoing restorative proctocolectomy for ulcerative colitis. Therapeutic attempts include manipulations of pouch flora composition. In this review, we bring together the evidence supporting the use of probiotics and prebiotics in pouchitis patients, to clarify the place of these treatments in current therapeutic regimens.
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Affiliation(s)
- Lev Lichtenstein
- Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel.
| | - Irit Avni-Biron
- Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Ofer Ben-Bassat
- Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
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Yao CK, Muir JG, Gibson PR. Review article: insights into colonic protein fermentation, its modulation and potential health implications. Aliment Pharmacol Ther 2016; 43:181-196. [PMID: 26527169 DOI: 10.1111/apt.13456] [Citation(s) in RCA: 289] [Impact Index Per Article: 32.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Revised: 09/11/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Beneficial effects of carbohydrate fermentation on gastrointestinal health are well established. Conversely, protein fermentation generates harmful metabolites but their relevance to gastrointestinal health is poorly understood. AIM To review the effects of increased protein fermentation on biomarkers of colonic health, factors influencing fermentative activity and potential for dietary modulation to minimise detrimental effects. METHODS A literature search was performed in PubMed, Medline, EMBASE and Google scholar for clinical and pre-clinical studies using search terms - 'dietary protein', 'fermentation', 'putrefaction', 'phenols', 'sulphide', 'branched-chain fatty acid', 'carbohydrate fermentation', 'gastrointestinal'. RESULTS High protein, reduced carbohydrate diets alter the colonic microbiome, favouring a potentially pathogenic and pro-inflammatory microbiota profile, decreased short-chain fatty acid production and increased ammonia, phenols and hydrogen sulphide concentrations. These metabolites largely compromise the colonic epithelium structure, causing mucosal inflammation but may also directly modulate the enteric nervous system and intestinal motility. Increased protein fermentation as a result of a high-protein intake can be attenuated by addition of oligosaccharides, resistant starch and nonstarch polysaccharides and a reduction in total protein or specifically, aromatic and sulphur-containing amino acids. These factors may have clinical importance as novel therapeutic approaches to problems, in which protein fermentation may be implicated, such as malodorous flatus, irritable bowel syndrome, ulcerative colitis and prevention of colorectal cancer. CONCLUSIONS The direct clinical relevance of excessive protein fermentation in the pathogenesis of irritable bowel syndrome, malodorous flatus and ulcerative colitis are underexplored. Manipulating dietary carbohydrate and protein intake have potential therapeutic applications in such settings and warrant further clinical studies.
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Affiliation(s)
- C K Yao
- Department of Gastroenterology, Monash University, Alfred Health, Melbourne, Vic., Australia
| | - J G Muir
- Department of Gastroenterology, Monash University, Alfred Health, Melbourne, Vic., Australia
| | - P R Gibson
- Department of Gastroenterology, Monash University, Alfred Health, Melbourne, Vic., Australia
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Boesmans L, Ramakers M, Arijs I, Windey K, Vanhove W, Schuit F, Rutgeerts P, Verbeke K, De Preter V. Inflammation-Induced Downregulation of Butyrate Uptake and Oxidation Is Not Caused by a Reduced Gene Expression. J Cell Physiol 2015; 230:418-26. [PMID: 25059646 DOI: 10.1002/jcp.24725] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2014] [Accepted: 07/21/2014] [Indexed: 11/08/2022]
Abstract
In ulcerative colitis (UC) the butyrate metabolism is impaired, leading to energy-deficiency in the colonic cells. The effect of inflammation on the butyrate metabolism was investigated. HT-29 cells were incubated with pro-inflammatory cytokines (TNF-α and/or IFN-γ) for 1 and 24 h. Cells were additionally stimulated with butyrate to investigate its anti-inflammatory potential. Butyrate uptake and oxidation were measured using (14)C-labeled butyrate. Gene expression of the butyrate metabolism enzymes, interleukin 8 (IL-8; inflammatory marker) and villin-1 (VIL-1; epithelial cell damage marker) was measured via quantitative RT-PCR. Significantly increased IL-8 expression and decreased VIL-1 expression after 24 h incubation with TNF-α and/or IFN-γ confirmed the presence of inflammation. These conditions induced a decrease of both butyrate uptake and oxidation, whereas the gene expression was not reduced. Simultaneous incubation with butyrate counteracted the reduced butyrate oxidation. In contrast, 1 h incubation with TNF-α induced a significant increased IL-8 expression and decreased butyrate uptake. Incubation with TNF-α and/or IFN-γ for 1 h did not induce cell damage nor influence butyrate oxidation. The inflammation-induced downregulation of the butyrate metabolism was not caused by a reduced gene expression, but appeared consequential to a decreased butyrate uptake. Increasing the luminal butyrate levels might have therapeutic potential in UC.
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Affiliation(s)
- Leen Boesmans
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Meine Ramakers
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Ingrid Arijs
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.,Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - Karen Windey
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Wiebe Vanhove
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Frans Schuit
- Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - Paul Rutgeerts
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Kristin Verbeke
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Vicky De Preter
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
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Bjerrum JT, Wang Y, Hao F, Coskun M, Ludwig C, Günther U, Nielsen OH. Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn's disease and healthy individuals. Metabolomics 2015; 11:122-133. [PMID: 25598765 PMCID: PMC4289537 DOI: 10.1007/s11306-014-0677-3] [Citation(s) in RCA: 185] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Accepted: 05/14/2014] [Indexed: 12/12/2022]
Abstract
This study employs spectroscopy-based metabolic profiling of fecal extracts from healthy subjects and patients with active or inactive ulcerative colitis (UC) and Crohn's disease (CD) to substantiate the potential use of spectroscopy as a non-invasive diagnostic tool and to characterize the fecal metabolome in inflammatory bowel disease (IBD). Stool samples from 113 individuals (UC 48, CD 44, controls 21) were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with principal component analysis and orthogonal-projection to latent structure-discriminant analysis using SIMCA-P + 12 and MATLAB. Significant differences were found in the metabolic profiles making it possible to differentiate between active IBD and controls and between UC and CD. The metabolites holding differential power primarily belonged to a range of amino acids, microbiota-related short chain fatty acids, and lactate suggestive of an inflammation-driven malabsorption and dysbiosis of the normal bacterial ecology. However, removal of patients with intestinal surgery and anti-TNF-α antibody treatment eliminated the discriminative power regarding UC versus CD. This study consequently demonstrates that 1H NMR spectroscopy of fecal extracts is a potential non-invasive diagnostic tool and able to characterize the inflammation-driven changes in the metabolic profiles related to malabsorption and dysbiosis. Intestinal surgery and medication are to be accounted for in future studies, as it seems to be factors of importance in the discriminative process.
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Affiliation(s)
- Jacob Tveiten Bjerrum
| | - Yulan Wang
| | - Fuhua Hao
| | - Mehmet Coskun
| | - Christian Ludwig
| | - Ulrich Günther
| | - Ole Haagen Nielsen
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Abstract
PURPOSE OF REVIEW Pouchitis, representing a spectrum of disease phenotypes, is the most common long-term complication in patients who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Its management and prevention are challenging. RECENT FINDINGS Treatment modalities vary according to phenotypes of pouchitis. The medical therapy of pouchitis remains largely empiric and antibiotic-based. However, patients may develop de-novo chronic antibiotic-refractory pouchitis (CARP) or progress from acute antibiotic-responsive phenotype. Patients with CARP often require alternative medical approaches to routine antibiotics, including the use of oral or topical mesalazine, corticosteroids, and sometimes immunomodulators or biological agents against tumour necrosis factor. There are two strategies to prevent pouchitis, the primary (i.e., the prevention of the initial episode) and secondary (i.e., the prevention of recurrent episodes) prophylaxis. There are scant data in the literature on nutritional aspects. SUMMARY We evaluated the efficacy of current strategies of prevention and treatments of pouchitis and propose algorithms, including attention to nutrition wherein data exist.
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Affiliation(s)
- Zhaoxiu Liu
- aDepartment of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China bDepartment of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA cDepartment of General Surgery, Qidong City Hospital, Jiangsu, China
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Ianco O, Tulchinsky H, Lusthaus M, Ofer A, Santo E, Vaisman N, Dotan I. Diet of patients after pouch surgery may affect pouch inflammation. World J Gastroenterol 2013; 19:6458-6464. [PMID: 24151365 PMCID: PMC3801317 DOI: 10.3748/wjg.v19.i38.6458] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 08/06/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the diet of pouch patients compared to healthy controls, and to correlate pouch patients’ diet with disease behavior.
METHODS: Pouch patients were recruited and prospectively followed-up at the Comprehensive Pouch Clinic at the Tel Aviv Sourasky Medical Center. Pouch behavior was determined based on clinical, endoscopic and histological criteria. Healthy age- and sex-matched volunteers were selected from the “MABAT” Israeli Nutrition and Public Health Governmental Study and served as the control group. All the participants completed a 106-item food frequency questionnaire categorized into food groups and nutritional values based on those used in the United States Department of Agriculture food pyramid and the Israeli food pyramid. Data on Dietary behavior, food avoidance, the use of nutritional supplements, physical activity, smoking habits, and body-mass index (BMI) were also obtained. Pouch patients who had familial adenomatous polyposis (n = 3), irritable pouch syndrome (n = 4), or patients whose pouch surgery took place less than one year previously (n = 5) were excluded from analysis.
RESULTS: The pouch patients (n = 80) consumed significantly more from the bakery products food group (1.2 ± 1.4 servings/d vs 0.6 ± 1.1 servings/d, P < 0.05) and as twice as many servings from the oils and fats (4.8 ± 3.4 servings/d vs 2.4 ± 2 servings/d, P < 0.05), and the nuts and seeds food group (0.3 ± 0.6 servings/d vs 0.1 ± 0.4 servings/d, P < 0.05) compared to the controls (n = 80). The pouch patients consumed significantly more total fat (97.6 ± 40.5 g/d vs 84.4 ± 39 g/d, P < 0.05) and fat components [monounsaturated fatty acids (38.4 ± 16.4 g/d vs 30 ± 14 g/d, P < 0.001), and saturated fatty acids (30 ± 15.5 g/d vs 28 ± 14.1 g/d, P < 0.00)] than the controls. In contrast, the pouch patients consumed significantly fewer carbohydrates (305.5 ± 141.4 g/d vs 369 ± 215.2 g/d, P = 0.03), sugars (124 ± 76.2 g/d vs 157.5 ± 90.4 g/d, P = 0.01), theobromine (77.8 ± 100 mg/d vs 236.6 ± 244.5 mg/d, P < 0.00), retinol (474.4 ± 337.1 μg/d vs 832.4 ± 609.6 μg/d, P < 0.001) and dietary fibers (26.2 ± 15.4 g/d vs 30.7 ± 14 g/d, P = 0.05) than the controls. Comparisons of the food consumption of the patients without (n = 23) and with pouchitis (n = 45) showed that the former consumed twice as many fruit servings as the latter (3.6 ± 4.1 servings/d vs 1.8 ± 1.7 servings/d, respectively, P < 0.05). In addition, the pouchitis patients consumed significantly fewer liposoluble antioxidants, such as cryptoxanthin (399 ± 485 μg/d vs 890.1 ± 1296.8 μg/d, P < 0.05) and lycopene (6533.1 ± 6065.7 μg/d vs 10725.7 ± 10065.9 μg/d, P < 0.05), and less vitamin A (893.3 ± 516 μg/d vs 1237.5 ± 728 μg/d, P < 0.05) and vitamin C (153.3 ± 130 mg/d vs 285.3 ± 326.3 mg/d, P < 0.05) than the patients without pouchitis. The mean BMI of the pouchitis patients was significantly lower than the BMI of the patients with a normal pouch: 22.6 ± 3.2 vs 27 ± 4.9 (P < 0.001).
CONCLUSION: Decreased consumption of antioxidants by patients with pouchitis may expose them to the effects of inflammatory and oxidative stress and contribute to the development of pouchitis.
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Pathobiology and potential therapeutic value of intestinal short-chain fatty acids in gut inflammation and obesity. Dig Dis Sci 2013; 58:2756-66. [PMID: 23839339 PMCID: PMC4317286 DOI: 10.1007/s10620-013-2744-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Accepted: 06/03/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND The lumen of the gastrointestinal tract contains many substances produced from the breakdown of foodstuffs, from salivary, esophageal, intestinal, hepatic, and pancreatic secretions, and from sloughed cells present in the gastrointestinal lumen. Although these substances were traditionally regarded as waste products, there is increasing realization that many can be biologically active, either as signalling compounds or as nutrients. For example, proteins are broken down into amino acids, which are then sensed by nutrient receptors. The gut microbiome, which is at highest abundance in the ileocecum, has powerful metabolic activity, digesting and breaking down unabsorbed carbohydrates, proteins, and other ingested nutrients into phenols, amines, volatile organic compounds, methane, carbon dioxide, hydrogen, and hydrogen sulfide into volatile fatty acids, also called short-chain fatty acids (SCFAs). CONCLUSION These latter substances are the topic of this review. In this review, we will briefly discuss recent advances in the understanding SCFA production, signalling, and absorption, followed by a detailed description and discussion of trials of SCFAs, probiotics, and prebiotics in the treatment of gastrointestinal disease, in particular ulcerative colitis (UC), pouchitis, short bowel syndrome, and obesity.
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De Preter V, Rutgeerts P, Schuit F, Verbeke K, Arijs I. Impaired expression of genes involved in the butyrate oxidation pathway in Crohn's disease patients. Inflamm Bowel Dis 2013; 19:E43-4. [PMID: 22508661 DOI: 10.1002/ibd.22970] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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De Preter V, Arijs I, Windey K, Vanhove W, Vermeire S, Schuit F, Rutgeerts P, Verbeke K. Decreased mucosal sulfide detoxification is related to an impaired butyrate oxidation in ulcerative colitis. Inflamm Bowel Dis 2012; 18:2371-80. [PMID: 22434643 DOI: 10.1002/ibd.22949] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Accepted: 02/21/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Defective detoxification of sulfides leads to damage to the mucosa and may play a role in the etiology of ulcerative colitis (UC). The colonic mucosal thiosulfate sulfurtransferase (TST) enzyme removes H(2) S by conversion to the less toxic thiocyanate. In this study we measured colonic mucosal TST enzyme activity and gene expression in UC and controls. In addition, the influence of sulfides on butyrate oxidation was evaluated. METHODS Colonic mucosal biopsies were collected from 92 UC patients and 24 controls. TST activity was measured spectrophotometrically. To assess gene expression, total RNA from biopsies was used for quantitative reverse-transcription polymerase chain reaction (RT-PCR). In 20 UC patients, gene expression was reassessed after their first treatment with infliximab. To evaluate the effect of sulfides on butyrate oxidation, biopsies were incubated with 1.5 mM NaHS. RESULTS TST enzyme activity and gene expression were significantly decreased in UC patients vs. controls (P < 0.001). UC patients, classified into disease activity subgroups, showed a significantly decreased TST activity and gene expression in the subgroups as compared to healthy subjects (P < 0.05 for all). In 20 patients, gene expression was reassessed after their first infliximab therapy. In responders to infliximab, a significant increase in TST gene expression was observed. However, TST mRNA levels did not return to control values after therapy in the responders. In controls, but not in UC, sulfide significantly decreased butyrate oxidation. CONCLUSIONS We found an impaired detoxification mechanism of sulfide at TST protein and RNA level in UC. Inflammation was clearly associated with the observed TST deficiency.
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Affiliation(s)
- Vicky De Preter
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
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21
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De Preter V, Arijs I, Windey K, Vanhove W, Vermeire S, Schuit F, Rutgeerts P, Verbeke K. Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway. Inflamm Bowel Dis 2012; 18:1127-36. [PMID: 21987487 DOI: 10.1002/ibd.21894] [Citation(s) in RCA: 96] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2011] [Accepted: 08/17/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND In ulcerative colitis (UC) butyrate metabolism is impaired due to a defect in the butyrate oxidation pathway and/or transport. In the present study we correlated butyrate uptake and oxidation to the gene expression of the butyrate transporter SLC16A1 and the enzymes involved in butyrate oxidation (ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2) in UC and controls. METHODS Colonic mucosal biopsies were collected during endoscopy of 88 UC patients and 20 controls with normal colonoscopy. Butyrate uptake and oxidation was measured by incubating biopsies with (14) C-labeled Na-butyrate. To assess gene expression, total RNA from biopsies was used for quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In 20 UC patients, gene expression was reassessed after treatment with infliximab. RESULTS Butyrate uptake and oxidation were significantly decreased in UC versus controls (P < 0.001 for both). Butyrate oxidation remained significantly reduced in UC after correction for butyrate uptake (P < 0.001), suggesting that the butyrate oxidation pathway itself is also affected. Also, the mucosal gene expression of SLC16A1, ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2 was significantly decreased in UC as compared with controls (P < 0.001 for all). In a subgroup of patients (n = 20), the gene expression was reassessed after infliximab therapy. In responders to therapy, a significant increase in gene expression was observed. Nevertheless, only ACSM3 mRNA levels returned to control values after therapy in the responders groups. CONCLUSIONS The deficiency in the colonic butyrate metabolism in UC is initiated at the gene expression level and is the result of a decreased expression of SLC16A1 and enzymes in the β-oxidation pathway of butyrate.
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Affiliation(s)
- Vicky De Preter
- Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, K.U. Leuven, Leuven, Belgium
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Landy J, Al-Hassi HO, McLaughlin SD, Knight SC, Ciclitira PJ, Nicholls RJ, Clark SK, Hart AL. Etiology of pouchitis. Inflamm Bowel Dis 2012; 18:1146-55. [PMID: 22021180 DOI: 10.1002/ibd.21911] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Accepted: 09/06/2011] [Indexed: 12/16/2022]
Abstract
Restorative proctocolectomy with ileal-pouch anal anastomosis (RPC) is the operation of choice for ulcerative colitis (UC) patients requiring surgery. It is also used for patients with familial adenomatous polyposis (FAP). Pouchitis accounts for 10% of pouch failures. It is an idiopathic inflammatory condition that may occur in up to 50% of patients after RPC for UC. It is rarely seen in FAP patients after RPC. The etiology of pouchitis remains unclear. An overlap with UC is suggested by the frequency with which pouchitis affects patients with UC compared with FAP patients. There is significant clinical evidence implicating bacteria in the pathogenesis of pouchitis. Studies using culture and molecular methods demonstrate a dysbiosis of the pouch microbiota in pouchitis. Risk factors, genetic associations, and serological markers of pouchitis suggest that the interactions between the host immune responses and the pouch microbiota underlie the etiology of this idiopathic inflammatory condition. Here we present a detailed review of the data focusing on the pouch microbiota and the immune responses that support this hypothesis. We also discuss the contribution of luminal metabolic factors and the epithelial membrane in the etiology of this inflammatory process. The ileoanal pouch offers a unique opportunity to study the inter-relationships between the gut microbiota and host immune responses from before the onset of disease. For this reason the study of pouchitis could serve as a human model that significantly enhances our understanding of inflammatory bowel diseases in general.
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Affiliation(s)
- J Landy
- Department of Gastroenterology St Mark's Hospital, Harrow, London, UK
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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the majority of patients with ulcerative colitis who require surgical treatment. Pouchitis, the most common long-term complication of the procedure, involves a spectrum of disease processes with heterogeneous risk factors, clinical features, disease courses and prognoses. In addition, clinical symptoms of pouchitis are not specific and often overlap with those of other inflammatory and functional pouch disorders, such as Crohn's disease of the pouch and irritable pouch syndrome. Pouchoscopy and biopsy, along with laboratory and radiographic evaluations, are often required for accurate diagnosis in patients with symptoms indicative of pouchitis. Dysbiosis has been implicated as a triggering factor for pouchitis, and concurrent infection with pathogens, such as Clostridium difficile, might contribute to disease relapse and exacerbation. Antibiotic therapy is the main treatment modality. However, the management of antibiotic-dependent and antibiotic-refractory pouchitis remains challenging. Secondary causes of pouchitis, such as ischaemia, NSAID use, the presence of concurrent primary sclerosing cholangitis and other systemic immune-mediated disorders, should be evaluated and properly managed.
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24
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De Preter V, Geboes KP, Bulteel V, Vandermeulen G, Suenaert P, Rutgeerts P, Verbeke K. Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the β-oxidation pathway. Aliment Pharmacol Ther 2011; 34:526-32. [PMID: 21707682 DOI: 10.1111/j.1365-2036.2011.04757.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Butyrate, a colonic metabolite of carbohydrates, is considered as the major energy source for the colonic mucosa. An impaired butyrate metabolism has been reported in ulcerative colitis (UC), however, the cause still remains unknown. AIM In the present study, we investigated whether higher butyrate concentrations could normalise the oxidation rate in UC. Furthermore, it was investigated whether carnitine could enhance the butyrate oxidation. METHODS Mucosal biopsies from a total of 26 UC patients and 25 controls were incubated with (14)C-labelled Na-butyrate and the produced (14)CO(2) was measured. First, the rate of oxidative metabolism was compared at three different concentrations of Na-butyrate (0.05 mm, 1 mm and 10 mm). Then, incubations of biopsies were performed with carnitine alone or combined with ATP. RESULTS Overall, butyrate oxidation in UC was significantly lower than that in controls. The maximum rate of butyrate oxidation was achieved in UC and control subjects from 1 mm onwards. Increasing the butyrate concentration to a level to be present in the colonic lumen, i.e. 10 mm, did not increase the rate of butyrate oxidation in UC to the rate observed in controls. Addition of carnitine alone or combined with ATP caused no effects. CONCLUSIONS Saturation of butyrate kinetics was achieved from 1 mm in UC and control subjects. The rate of butyrate metabolism was significantly impaired in active ulcerative colitis. The addition of compounds interfering with the β-oxidation pathway had no effect on the butyrate metabolism in UC.
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Affiliation(s)
- V De Preter
- Translational Research Center for Gastrointestinal Disorders, KULeuven, Belgium
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Lepage P, Häsler R, Spehlmann ME, Rehman A, Zvirbliene A, Begun A, Ott S, Kupcinskas L, Doré J, Raedler A, Schreiber S. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 2011; 141:227-36. [PMID: 21621540 DOI: 10.1053/j.gastro.2011.04.011] [Citation(s) in RCA: 451] [Impact Index Per Article: 32.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2010] [Revised: 04/02/2011] [Accepted: 04/08/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Interactions between genetic and environmental factors are believed to be involved in onset and initiation of inflammatory bowel disease. We analyzed the interaction between gastrointestinal mucosal microbiota and host genes in twin pairs discordant for ulcerative colitis (UC) to study the functional interaction between microbiota and mucosal epithelium. METHODS Biopsy were collected from sigmoid colon of UC patients and their healthy twins (discordant twin pairs) and from twins without UC. Microbiota profiles were determined from analysis of 16S ribosomal DNA libraries; messenger RNA profiles were determined by microarray analysis. RESULTS Patients with UC had dysbiotic microbiota, characterized by less bacterial diversity and more Actinobacteria and Proteobacteria than that of their healthy siblings; healthy siblings from discordant twins had more bacteria from the Lachnospiraceae and Ruminococcaceae families than twins who were both healthy. In twins who were both healthy, 34 mucosal transcripts correlated with bacterial genera, whereas only 25 and 11 correlated with bacteria genera in healthy individuals and their twins with UC, respectively. Transcripts related to oxidative and immune responses were differentially expressed between patients with UC and their healthy twins. CONCLUSIONS The transcriptional profile of the mucosa appears to interact with the colonic microbiota; this interaction appears to be lost in colon of patients with UC. Bacterial functions, such as butyrate production, might affect mucosal gene expression. Patients with UC had different gene expression profiles and lower levels of biodiversity than their healthy twins, as well as unusual aerobic bacteria. Patients with UC had lower percentages of potentially protective bacterial species than their healthy twins.
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Affiliation(s)
- Patricia Lepage
- Institute of Clinical Molecular Biology, Christian-Albrechts University-Kiel, Kiel, Germany
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Benharush D, Cohen MJ, Kasirer Y, Turner D. Short chain fatty acids (butyrate) for induction of remission in ulcerative colitis. Hippokratia 2010. [DOI: 10.1002/14651858.cd008730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- David Benharush
- The Hebrew University; Faculty of Medicine; Jerusalem Israel
| | - Matan J Cohen
- Hadassah Medical Center; Center for Clinical Quality & Safety; Ein Kessem Campus Box 53, POB12000 Jerusalem Israel 91120
| | - Yair Kasirer
- Shaare Zedek Medical Center; Pediatric Gastroenterology Unit; P.O.B 3235 Jerusalem 91031 Israel
| | - Dan Turner
- Shaare Zedek Medical Center; Pediatric Gastroenterology Unit; P.O.B 3235 Jerusalem 91031 Israel
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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for most patients with ulcerative colitis who require surgery. Although the surgical procedure offers a cure in some patients, postoperative inflammatory and noninflammatory complications are common. Pouchitis is the most common long-term complication of the procedure. Pouchitis represents a spectrum of disease processes with heterogeneous risk factors, clinical phenotypes, natural history, and prognosis. Accurate diagnosis and classification are important for proper treatment and prognosis.
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Affiliation(s)
- Hao Wu
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China
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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for most patients with ulcerative colitis who require surgery. Although the surgical procedure offers a cure in some patients, postoperative inflammatory and noninflammatory complications are common. Pouchitis is the most common long-term complication of the procedure. Pouchitis represents a spectrum of disease processes with heterogeneous risk factors, clinical phenotypes, natural history, and prognosis. Accurate diagnosis and classification are important for proper treatment and prognosis.
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Affiliation(s)
- Hao Wu
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China
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Navaneethan U, Shen B. Laboratory tests for patients with ileal pouch-anal anastomosis: clinical utility in predicting, diagnosing, and monitoring pouch disorders. Am J Gastroenterol 2009; 104:2606-15. [PMID: 19603012 DOI: 10.1038/ajg.2009.392] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC-associated dysplasia, and for the majority of patients with familial adenomatous polyposis. Pouchitis and other complications of IPAA are common. There are scant data on laboratory markers for the evaluation and diagnosis of pouch disorders. The presence of immunogenotypic markers such as genetic polymorphisms of interleukin-1 (IL-1) receptor antagonist, NOD2/CARD15, Toll-like receptor, and tumor necrosis factor-alpha has been reported to be associated with pouchitis. Immunophenotypic/serologic markers such as perinuclear antineutrophil cytoplasmic antibody and anti-CBir1 have been investigated as possible markers for predicting and diagnosing pouchitis. Fecal markers including lactoferrin and calprotectin seem to be useful in distinguishing inflammatory from noninflammatory pouch disorders. In our practice, we have encountered a large number of pouch patients with Clostridium difficile infection. Laboratory evaluation provides information on the etiology and pathogenesis of pouchitis, and it also helps practicing clinicians with accurate diagnosis, differential diagnosis, disease stratification, and management of ileal pouch disorders.
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Affiliation(s)
- Udayakumar Navaneethan
- The Pouchitis Clinic, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
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