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      Microbial Population Changes and Their Relationship with Human Health and Disease

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          Abstract

          Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.

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          Most cited references107

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          Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

          The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis.
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            Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

            The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.
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              Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis.

              Several case series have reported the effects of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). We assessed the efficacy and safety of FMT for patients with UC in a double-blind randomized trial. Patients with mild to moderately active UC (n = 50) were assigned to groups that underwent FMT with feces from healthy donors or were given autologous fecal microbiota (control); each transplant was administered via nasoduodenal tube at the start of the study and 3 weeks later. The study was performed at the Academic Medical Center in Amsterdam from June 2011 through May 2014. The composite primary end point was clinical remission (simple clinical colitis activity index scores ≤2) combined with ≥1-point decrease in the Mayo endoscopic score at week 12. Secondary end points were safety and microbiota composition by phylogenetic microarray in fecal samples. Thirty-seven patients completed the primary end point assessment. In the intention-to-treat analysis, 7 of 23 patients who received fecal transplants from healthy donors (30.4%) and 5 of 25 controls (20.0%) achieved the primary end point (P = .51). In the per-protocol analysis, 7 of 17 patients who received fecal transplants from healthy donors (41.2%) and 5 of 20 controls (25.0%) achieved the primary end point (P = .29). Serious adverse events occurred in 4 patients (2 in the FMT group), but these were not considered to be related to the FMT. At 12 weeks, the microbiota of responders in the FMT group was similar to that of their healthy donors; remission was associated with proportions of Clostridium clusters IV and XIVa. In this phase 2 trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors and those who received their own fecal microbiota, which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. ClinicalTrials.gov Number: NCT01650038. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                03 March 2019
                March 2019
                : 7
                : 3
                : 68
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain; croblesan@ 123456hotmail.com (C.R.-S.); fontana@ 123456ugr.es (L.F.)
                [2 ]Institute of Nutrition and Food Technology “José Mataix,” Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain; miguelno@ 123456ugr.es
                [3 ]Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
                [4 ]Department of Biochemistry and Molecular Biology I, School of Sciences, University of Granada, 18071 Granada, Spain; mjsaez@ 123456ugr.es
                [5 ]Departamento de Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile; chechomu@ 123456hotmail.com
                [6 ]National Agency for Medicines (ANAMED), Public Health Institute, Santiago 7780050, Chile
                [7 ]Department of Cell Biology, School of Sciences, University of Granada, 18071 Granada, Spain
                Author notes
                [* ]Correspondence: analvarezmercado@ 123456gmail.com (A.I.A.-M.); jrplaza@ 123456ugr.es (J.P.-D.); fmolina@ 123456ugr.es (F.A.-M.); Tel.: +34-9-5824-1000 (ext. 41599) (J.P.-D.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8476-9970
                https://orcid.org/0000-0002-5171-9408
                https://orcid.org/0000-0001-7439-9817
                https://orcid.org/0000-0001-8395-8393
                Article
                microorganisms-07-00068
                10.3390/microorganisms7030068
                6463060
                30832423
                0d567773-1aca-45a4-8626-963e7622845c
                © 2019 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
                : 30 January 2019
                : 27 February 2019
                Categories
                Review

                gut microbiota,microbial population changes,randomized clinical trial,health status,obesity,non-communicable diseases,non-alcoholic fatty liver disease,inflammatory bowel disease

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