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      The Role of Gut Microbiota in Atherosclerosis and Hypertension

      review-article
      , *
      Frontiers in Pharmacology
      Frontiers Media S.A.
      gut microbiota, cardiovascular disease, atherosclerosis, TMAO, bile acids, hypertension, SCFAs

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          Abstract

          In recent years, accumulating evidence has indicated the importance of gut microbiota in maintaining human health. Gut dysbiosis is associated with the pathogenesis of a number of metabolic diseases including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVDs). Indeed, CVD has become the leading cause of death worldwide, especially in developed countries. In this review, we mainly discuss the gut microbiota-involved mechanisms of CVD focusing on atherosclerosis and hypertension, two major risk factors for serious CVD. Then, we briefly discuss the prospects of gut microbiota-targeted therapeutic strategies for the treatment of CVD in the future.

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          Most cited references94

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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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            Identification of a nuclear receptor for bile acids.

            Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.
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              Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine.

              Seven strains of Roseburia sp., Faecalibacterium prausnitzii, and Coprococcus sp. from the human gut that produce high levels of butyric acid in vitro were studied with respect to key butyrate pathway enzymes and fermentation patterns. Strains of Roseburia sp. and F. prausnitzii possessed butyryl coenzyme A (CoA):acetate-CoA transferase and acetate kinase activities, but butyrate kinase activity was not detectable either in growing or in stationary-phase cultures. Although unable to use acetate as a sole source of energy, these strains showed net utilization of acetate during growth on glucose. In contrast, Coprococcus sp. strain L2-50 is a net producer of acetate and possessed detectable butyrate kinase, acetate kinase, and butyryl-CoA:acetate-CoA transferase activities. These results demonstrate that different functionally distinct groups of butyrate-producing bacteria are present in the human large intestine.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                25 September 2018
                2018
                : 9
                : 1082
                Affiliations
                Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine , Shanghai, China
                Author notes

                Edited by: Li-Long Pan, Fudan University, China

                Reviewed by: Martina Montagnana, Università degli Studi di Verona, Italy; Ru Yan, University of Macau, Macau

                *Correspondence: Houkai Li, houkai1976@ 123456126.com

                This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.01082
                6167910
                30319417
                9ba7c552-2065-40b1-b746-3117181742b8
                Copyright © 2018 Ma and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 May 2018
                : 06 September 2018
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 174, Pages: 14, Words: 0
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                gut microbiota,cardiovascular disease,atherosclerosis,tmao,bile acids,hypertension,scfas

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