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      About Digestion: 3.2 Impact Factor I 6.4 CiteScore I 0.914 Scimago Journal & Country Rank (SJR)

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      Physiological Role of Gut Microbiota for Maintaining Human Health

      review-article
      *
      Digestion
      S. Karger AG
      Short-chain fatty acids, Bacteroides , Firmicutes, Butyrate

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: The human body is colonized by an extremely complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. Recent studies have focused on the link between these microbes and our health. Summary: Diet contributes to shaping the gut microbial structure and influences metabolic functions of the host. Alteration of the microbial structure and function (dysbiosis) is associated with the pathogenesis of various disorders. Fermentation is the process by which anaerobic bacteria (Firmicutes and Bacteroidetes) break down indigestible carbohydrates to short-chain fatty acids (SCFAs; acetate, propionate and butyrate), collaborating with species specialized in oligosaccharide fermentation (e.g. Bifidobacteria). Butyrate and propionate can regulate intestinal physiology and immune function, while acetate acts as a substrate for lipogenesis and gluconeogenesis. The gut microbiota regulates immune homeostasis via the induction of regulatory T cells and Th17 cells. In addition, butyrate has strong anti-inflammatory effects possibly through the inhibition of histone deacetylase activity. Metabolic products generated by the gut microbiota, such as SCFAs, GABA, tryptophan, serotonin and catecholamine, transmit a signal to resident cells in the gut. Key Message: Advances made in the DNA sequencing technology and bioinformatics have revolutionized our understanding of the microbes in the gut.

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          Most cited references18

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          IL-17 family cytokines and the expanding diversity of effector T cell lineages.

          Since its conception two decades ago, the Th1-Th2 paradigm has provided a framework for understanding T cell biology and the interplay of innate and adaptive immunity. Naive T cells differentiate into effector T cells with enhanced functional potential for orchestrating pathogen clearance largely under the guidance of cytokines produced by cells of the innate immune system that have been activated by recognition of those pathogens. This secondary education of post-thymic T cells provides a mechanism for appropriately matching adaptive immunity to frontline cues of the innate immune system. Owing in part to the rapid identification of novel cytokines of the IL-17 and IL-12 families using database searches, the factors that specify differentiation of a new effector T cell lineage-Th17-have now been identified, providing a new arm of adaptive immunity and presenting a unifying model that can explain many heretofore confusing aspects of immune regulation, immune pathogenesis, and host defense.
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            The role of pH in determining the species composition of the human colonic microbiota.

            The pH of the colonic lumen varies with anatomical site and microbial fermentation of dietary residue. We have investigated the impact of mildly acidic pH, which occurs in the proximal colon, on the growth of different species of human colonic bacteria in pure culture and in the complete microbial community. Growth was determined for 33 representative human colonic bacteria at three initial pH values (approximately 5.5, 6.2 and 6.7) in anaerobic YCFA medium, which includes a mixture of short-chain fatty acids (SCFA) with 0.2% glucose as energy source. Representatives of all eight Bacteroides species tested grew poorly at pH 5.5, as did Escherichia coli, whereas 19 of the 23 gram-positive anaerobes tested gave growth rates at pH 5.5 that were at least 50% of those at pH 6.7. Growth inhibition of B. thetaiotaomicron at pH 5.5 was increased by the presence of the SCFA mix (33 mM acetate, 9 mM propionate and 1 mM each of iso-valerate, valerate and iso-butyrate). Analysis of amplified 16S rRNA sequences demonstrated a major pH-driven shift within a human faecal bacterial community in a continuous flow fermentor. Bacteroides spp. accounted for 27% of 16S rRNA sequences detected at pH 5.5, but 86% of sequences at pH 6.7. Conversely, butyrate-producing gram-positive bacteria related to Eubacterium rectale represented 50% of all 16S rRNA sequences at pH 5.5, but were not detected at pH 6.7. Inhibition of the growth of a major group of gram-negative bacteria at mildly acidic pH apparently creates niches that can be exploited by more low pH-tolerant microorganisms.
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              GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes.

              The expression of short-chain fatty acid receptors GPR41/FFAR3 and GPR43/ free fatty acid receptor 2 (FFAR2) was studied in the gastrointestinal tract of transgenic monomeric red fluorescent protein (mRFP) reporter mice. In the stomach free fatty acid receptor 3 (FFAR3)-mRFP was expressed in a subpopulation of ghrelin and gastrin cells. In contrast, strong expression of FFAR3-mRFP was observed in all cholecystokinin, glucose-dependent insulinotropic peptide (GIP), and secretin cells of the proximal small intestine and in all glucagon-like peptide-1 (GLP-1), peptide YY, and neurotensin cells of the distal small intestine. Throughout the colon and rectum, FFAR3-mRFP was strongly expressed in the large population of peptide YY and GLP-1 cells and in the neurotensin cells of the proximal colon. A gradient of expression of FFAR3-mRFP was observed in the somatostatin cells from less than 5% in the stomach to more than 95% in the rectum. Substance P-containing enterochromaffin cells displayed a similar gradient of FFAR3-mRFP expression throughout the small intestine. Surprisingly, FFAR3-mRFP was also expressed in the neuronal cells of the submucosal and myenteric ganglia. Quantitative PCR analysis of fluorescence-activated cell sorting (FACS) purified FFAR3-mRFP positive cells confirmed the coexpression with the various peptide hormones as well as key neuronal marker proteins. The FFAR2-mRFP reporter was strongly expressed in a large population of leukocytes in the lamina propria of in particular the small intestine but surprisingly only weakly in a subpopulation of enteroendocrine cells. Nevertheless, synthetic ligands specific for either FFAR3 or FFAR2 each released GLP-1 from colonic crypt cultures and the FFAR2 agonist mobilized intracellular Ca²⁺ in FFAR2 positive enteroendocrine cells. It is concluded that FFAR3-mRFP serves as a useful marker for the majority of enteroendocrine cells of the small and large intestine and that FFAR3 and FFAR2 both act as sensors for short-chain fatty acids in enteroendocrine cells, whereas FFAR3 apparently has this role alone in enteric neurons and FFAR2 in enteric leukocytes.
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                Author and article information

                Journal
                DIG
                Digestion
                10.1159/issn.0012-2823
                Digestion
                S. Karger AG
                0012-2823
                1421-9867
                2016
                June 2016
                09 February 2016
                : 93
                : 3
                : 176-181
                Affiliations
                Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Japan
                Author notes
                *Akira Andoh, MD, PhD, Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192 (Japan), E-Mail andoh@belle.shiga-med.ac.jp
                Article
                444066 Digestion 2016;93:176-181
                10.1159/000444066
                26859303
                c70e514e-5aa5-4970-8437-0f2348528e13
                © 2016 Japanese Gastroenterological Association Published by S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 14 January 2016
                : 14 January 2016
                Page count
                Figures: 2, References: 41, Pages: 6
                Categories
                JGA Topic Review

                Oncology & Radiotherapy,Gastroenterology & Hepatology,Surgery,Nutrition & Dietetics,Internal medicine
                Butyrate,Short-chain fatty acids,Firmicutes, Bacteroides

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