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      Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation

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          Abstract

          Ulcerative colitis (UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. However, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation (FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in the pathogenesis and treatment of UC.

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          Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

          Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.
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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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              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

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                7 January 2018
                7 January 2018
                : 24
                : 1
                : 5-14
                Affiliations
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China
                Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
                Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410008, Hunan Province, China. wangxiaoyan2913@ 123456126.com
                Author notes

                Author contributions: Shen ZH wrote the manuscript; Wang XY contributed to the manuscript critical revision; all authors approved the final version of the article.

                Correspondence to: Xiao-Yan Wang, MD, PhD, Professor, Department of Gastroenterology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, China. wangxiaoyan2913@ 123456126.com

                Telephone: +86-13974889301 Fax: +86-731-88618457

                Article
                jWJG.v24.i1.pg5
                10.3748/wjg.v24.i1.5
                5757125
                29358877
                cf9225cf-26de-4aab-ae75-bea5f191b16a
                ©The Author(s) 2018. 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
                : 1 October 2017
                : 7 November 2017
                : 21 November 2017
                Categories
                Review

                fecal microbiota transplantation,intestinal microbiota,ulcerative colitis,probiotics,mechanism,clinical application

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