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      Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism

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          Abstract

          Short-chain fatty acids (SCFAs), particularly acetate, propionate and butyrate, are mainly produced by anaerobic fermentation of gut microbes. SCFAs play an important role in regulating energy metabolism and energy supply, as well as maintaining the homeostasis of the intestinal environment. In recent years, many studies have shown that SCFAs demonstrate physiologically beneficial effects, and the signalling pathways related to SCFA production, absorption, metabolism, and intestinal effects have been discovered. Two major signalling pathways concerning SCFAs, G-protein-coupled receptors (GPRCs) and histone deacetylases (HDACs), are well recognized. In this review, we summarize the recent advances concerning the biological properties of SCFAs and the signalling pathways in inflammation and glucose and lipid metabolism.

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          Most cited references146

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          The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

          Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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            The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.

            Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.
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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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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                02 September 2020
                September 2020
                : 21
                : 17
                : 6356
                Affiliations
                [1 ]College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; hejin19960812@ 123456163.com (J.H.); sicau_zhangpeiwen@ 123456163.com (P.Z.); shenlinyuan0815@ 123456163.com (L.S.); dky9829@ 123456126.com (L.N.); tanya@ 123456stu.sicau.edu.cn (Y.T.); chenlei815918@ 123456sicau.edu.cn (L.C.); zhye3@ 123456foxmail.com (Y.Z.); blin16@ 123456126.com (L.B.); xiaoxia6363@ 123456126.com (X.H.); xuewei.li@ 123456sicau.edu.cn (X.L.)
                [2 ]Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
                [3 ]Institute of Animal Husbandry and Veterinary, Guizhou Academy of Agricultural Science, Guiyang 550005, China
                Author notes
                [* ]Correspondence: zhangsh1919@ 123456163.com (S.Z.); zhuli7508@ 123456163.com (L.Z.); Tel.: +86-28-8629-1133 (S.Z. & L.Z.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-6793-2588
                https://orcid.org/0000-0001-6072-3268
                Article
                ijms-21-06356
                10.3390/ijms21176356
                7503625
                32887215
                9864a230-ac69-471c-a0b7-13164fc48095
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 July 2020
                : 27 August 2020
                Categories
                Review

                Molecular biology
                short-chain fatty acids,inflammation,glycose and lipid metabolism,signalling pathways

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