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      Role of gut microbiota in cardiovascular diseases

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          Abstract

          The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.

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          Most cited references57

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          Dietary modulation of the human colonic microbiota: updating the concept of prebiotics.

          Prebiotics are non-digestible (by the host) food ingredients that have a beneficial effect through their selective metabolism in the intestinal tract. Key to this is the specificity of microbial changes. The present paper reviews the concept in terms of three criteria: (a) resistance to gastric acidity, hydrolysis by mammalian enzymes and gastrointestinal absorption; (b) fermentation by intestinal microflora; (c) selective stimulation of the growth and/or activity of intestinal bacteria associated with health and wellbeing. The conclusion is that prebiotics that currently fulfil these three criteria are fructo-oligosaccharides, galacto-oligosaccharides and lactulose, although promise does exist with several other dietary carbohydrates. Given the range of food vehicles that may be fortified by prebiotics, their ability to confer positive microflora changes and the health aspects that may accrue, it is important that robust technologies to assay functionality are used. This would include a molecular-based approach to determine flora changes. The future use of prebiotics may allow species-level changes in the microbiota, an extrapolation into genera other than the bifidobacteria and lactobacilli, and allow preferential use in disease-prone areas of the body.
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            No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.

            Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in subjects believed to have NCGS. We performed a double-blind cross-over trial of 37 subjects (aged 24-61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Participants were randomly assigned to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for 1 week, followed by a washout period of at least 2 weeks. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed over to groups given gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days. Symptoms were evaluated by visual analogue scales. In all participants, gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein. Gluten-specific effects were observed in only 8% of participants. There were no diet-specific changes in any biomarker. During the 3-day rechallenge, participants' symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed. In a placebo-controlled, cross-over rechallenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Fecal microbiota transplantation and emerging applications.

              Fecal microbiota transplantation (FMT) has been utilized sporadically for over 50 years. In the past few years, Clostridium difficile infection (CDI) epidemics in the USA and Europe have resulted in the increased use of FMT, given its high efficacy in eradicating CDI and associated symptoms. As more patients request treatment and more clinics incorporate FMT into their treatment repertoire, reports of applications outside of CDI are emerging, paving the way for the use of FMT in several idiopathic conditions. Interest in this therapy has largely been driven by new research into the gut microbiota, which is now beginning to be appreciated as a microbial human organ with important roles in immunity and energy metabolism. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of FMT for several disorders, including IBD, IBS, the metabolic syndrome, neurodevelopmental disorders, autoimmune diseases and allergic diseases, among others. The field of microbiota-related disorders is currently in its infancy; it certainly is an exciting time in the burgeoning science of FMT and we expect to see new and previously unexpected applications in the near future. Well-designed and well-executed randomized trials are now needed to further define these microbiota-related conditions.
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                Author and article information

                Contributors
                Journal
                World J Cardiol
                WJC
                World Journal of Cardiology
                Baishideng Publishing Group Inc
                1949-8462
                26 April 2020
                26 April 2020
                : 12
                : 4
                : 110-122
                Affiliations
                Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD 21215, United States
                Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD 21215, United States
                Department of Internal Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN 55905, United States
                Department of Internal Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN 55905, United States
                Department of Internal Medicine, Division of Hospital Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
                Department of Internal Medicine, Medical University of South Carolina/AnMed Campus, Charleston, SC 29425, United States
                Division of Endocrinology, Diabetes and Nutrition, Medical University of South Carolina/Anmed Campus, Anderson, SC 29621, United States
                Department of Internal Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN 55905, United States. chaudhary.rahul@ 123456mayo.edu
                Author notes

                Author contributions: Kingsley T, Kirchoff R and Chaudhary R proposed study conception and designed the study; Novakovic M, Rout A, Singh A and Verma V acquired the data; Novakovic M, Rout A, Kingsley T, Verma V, Kant R and Chaudhary R analyzed and interpreted the data; Novakovic M, Rout A, Kingsley T, Kirchoff R, Singh A, Kant R and Verma V drafted the manuscript; Singh A, Kant R and Chaudhary R revised the manuscript.

                Corresponding author: Rahul Chaudhary, MD, FACP, Doctor, Staff Physician, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. chaudhary.rahul@ 123456mayo.edu

                Article
                jWJC.v12.i4.pg110
                10.4330/wjc.v12.i4.110
                7215967
                32431782
                a06ab9f1-5d88-4723-ab23-8d93d2444d91
                ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 8 December 2019
                : 3 March 2020
                : 12 March 2020
                Categories
                Review

                cardiovascular disease,coronary artery disease,gut microbiota,dysbiosis,thrombosis

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