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      Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health

      review-article
      ,
      Microbiome
      BioMed Central
      Human gut microbiome, Microbial metabolism, Macronutrients, Human health

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          Abstract

          The human gut microbiome is a critical component of digestion, breaking down complex carbohydrates, proteins, and to a lesser extent fats that reach the lower gastrointestinal tract. This process results in a multitude of microbial metabolites that can act both locally and systemically (after being absorbed into the bloodstream). The impact of these biochemicals on human health is complex, as both potentially beneficial and potentially toxic metabolites can be yielded from such microbial pathways, and in some cases, these effects are dependent upon the metabolite concentration or organ locality. The aim of this review is to summarize our current knowledge of how macronutrient metabolism by the gut microbiome influences human health. Metabolites to be discussed include short-chain fatty acids and alcohols (mainly yielded from monosaccharides); ammonia, branched-chain fatty acids, amines, sulfur compounds, phenols, and indoles (derived from amino acids); glycerol and choline derivatives (obtained from the breakdown of lipids); and tertiary cycling of carbon dioxide and hydrogen. Key microbial taxa and related disease states will be referred to in each case, and knowledge gaps that could contribute to our understanding of overall human wellness will be identified.

          Electronic supplementary material

          The online version of this article (10.1186/s40168-019-0704-8) contains supplementary material, which is available to authorized users.

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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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            The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

            The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies.
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              Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health

              The colon is inhabited by a dense population of microorganisms, the so-called “gut microbiota,” able to ferment carbohydrates and proteins that escape absorption in the small intestine during digestion. This microbiota produces a wide range of metabolites, including short chain fatty acids (SCFA). These compounds are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids which can present straight or branched-chain conformation. Their production is influenced by the pattern of food intake and diet-mediated changes in the gut microbiota. SCFA have distinct physiological effects: they contribute to shaping the gut environment, influence the physiology of the colon, they can be used as energy sources by host cells and the intestinal microbiota and they also participate in different host-signaling mechanisms. We summarize the current knowledge about the production of SCFA, including bacterial cross-feedings interactions, and the biological properties of these metabolites with impact on the human health.
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                Author and article information

                Contributors
                koliphan@uoguelph.ca
                eav@uoguelph.ca
                Journal
                Microbiome
                Microbiome
                Microbiome
                BioMed Central (London )
                2049-2618
                13 June 2019
                13 June 2019
                2019
                : 7
                : 91
                Affiliations
                ISNI 0000 0004 1936 8198, GRID grid.34429.38, Department of Molecular and Cellular Biology, , University of Guelph, ; 50 Stone Rd E, Guelph, ON N1G 2W1 Canada
                Author information
                http://orcid.org/0000-0002-6921-7094
                Article
                704
                10.1186/s40168-019-0704-8
                6567490
                31196177
                831da3e3-8a2a-4aee-b716-a1cfb0872283
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 31 March 2019
                : 28 May 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 4R33AI121575-03
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                human gut microbiome,microbial metabolism,macronutrients,human health

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