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      Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers

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          Abstract

          These results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual’s microbiota in determining whether or not they respond to a specific dietary supplement. In particular, R. bromii or C. chartatabidum may be required for enhanced butyrate production in response to RS. Bifidobacteria, though proficient at degrading RS and inulin, may not contribute to the butyrogenic effect of those fermentable fibers in the short term.

          ABSTRACT

          Production of short-chain fatty acids (SCFAs), especially butyrate, in the gut microbiome is required for optimal health but is frequently limited by the lack of fermentable fiber in the diet. We attempted to increase butyrate production by supplementing the diets of 174 healthy young adults for 2 weeks with resistant starch from potatoes (RPS), resistant starch from maize (RMS), inulin from chicory root, or an accessible corn starch control. RPS resulted in the greatest increase in total SCFAs, including butyrate. Although the majority of microbiomes responded to RPS with increases in the relative abundance of bifidobacteria, those that responded with an increase in Ruminococcus bromii or Clostridium chartatabidum were more likely to yield higher butyrate concentrations, especially when their microbiota were replete with populations of the butyrate-producing species Eubacterium rectale. RMS and inulin induced different changes in fecal communities, but they did not generate significant increases in fecal butyrate levels.

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          Most cited references23

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          Formation of propionate and butyrate by the human colonic microbiota

          The human gut microbiota ferments dietary non-digestible carbohydrates into short-chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health-promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross-feeding of intermediary metabolites (in particular lactate, succinate and 1,2-propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.
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            Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease.

            Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NFkappaB), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression. Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NFkappaB p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NFkappaB inhibitory protein (IkappaBalpha) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis. Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NFkappaB from the cytoplasm to the nucleus. LPS induced NFkappaB transcriptional activity was decreased by butyrate while IkappaBalpha levels were stable. Butyrate treatment also improved TNBS induced colitis. Butyrate decreases proinflammatory cytokine expression via inhibition of NFkappaB activation and IkappaBalpha degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.
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              Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis.

              Cross-feeding is an important metabolic interaction mechanism of bacterial groups inhabiting the human colon and includes features such as the utilization of acetate by butyrate-producing bacteria as may occur between Bifidobacterium and Faecalibacterium genera. In this study, we assessed the utilization of different carbon sources (glucose, starch, inulin and fructooligosaccharides) by strains of both genera and selected the best suited combinations for evidencing this cross-feeding phenomenon. Co-cultures of Bifidobacterium adolescentis L2-32 with Faecalibacterium prausnitzii S3/L3 with fructooligosaccharides as carbon source, as well as with F. prausnitzii A2-165 in starch, were carried out and the production of short-chain fatty acids was determined. In both co-cultures, acetate levels decreased between 8 and 24 h of incubation and were lower than in the corresponding B. adolescentis monocultures. In contrast, butyrate concentrations were higher in co-cultures as compared to the respective F. prausnitzii monocultures, indicating enhanced formation of butyrate by F. prausnitzii in the presence of the bifidobacteria. Variations in the levels of acetate and butyrate were more pronounced in the co-culture with fructooligosaccharides than with starch. Our results provide a clear demonstration of cross-feeding between B. adolescentis and F. prausnitzii.
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                Author and article information

                Contributors
                Role: Editor
                Role: Solicited external reviewer
                Role: Solicited external reviewer
                Journal
                mBio
                MBio
                mbio
                mbio
                mBio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                29 January 2019
                Jan-Feb 2019
                : 10
                : 1
                : e02566-18
                Affiliations
                [a ]Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
                [b ]Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, USA
                New York University
                Baylor College of Medicine
                University of Alberta
                Author notes
                Address correspondence to Thomas M. Schmidt, schmidti@ 123456umich.edu .
                [*]

                Present address: Nielson T. Baxter, Elanco Animal Health, Greenfield, Indiana; Arvind Venkataraman, CF Biosciences, The Procter & Gamble Company, Cincinnati, Ohio.

                Author information
                https://orcid.org/0000-0002-8209-6055
                Article
                mBio02566-18
                10.1128/mBio.02566-18
                6355990
                30696735
                85ec5232-917b-472c-bc32-222175a1fc7b
                Copyright © 2019 Baxter et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 3 December 2018
                : 6 December 2018
                Page count
                supplementary-material: 1, Figures: 5, Tables: 1, Equations: 0, References: 45, Pages: 13, Words: 8321
                Funding
                Funded by: Howard Hughes Medical Institute (HHMI), https://doi.org/10.13039/100000011;
                Award ID: 52008119
                Award Recipient :
                Funded by: University of Michigan (U-M), https://doi.org/10.13039/100007270;
                Award ID: Host-Microbiome Initiative
                Award Recipient :
                Funded by: Procter and Gamble (P&G), https://doi.org/10.13039/100004357;
                Award Recipient :
                Categories
                Research Article
                Host-Microbe Biology
                Custom metadata
                January/February 2019

                Life sciences
                bifidobacteria,butyrate,microbiome,ruminococcus,scfa,prebiotic
                Life sciences
                bifidobacteria, butyrate, microbiome, ruminococcus, scfa, prebiotic

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