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      Protocol for Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

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      1 , , 1 , 2 ,
      BioMed Research International
      Hindawi

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          Abstract

          Background

          Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain.

          Aim

          To further study the efficacy and safety and protocol of FMT for IBD.

          Methods

          A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome.

          Results

          A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn's disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients ( P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003).

          Conclusion

          FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.

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          Most cited references43

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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
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                13 September 2018
                : 2018
                : 8941340
                Affiliations
                1Department of Gastroenterology and Hepatology, The Second Hospital of Anhui Medical University, Hefei, Anhui Province, China
                2Department of Pharmacology, Anhui Medical University, Hefei, Anhui Province, China
                Author notes

                Academic Editor: Gelin Xu

                Author information
                http://orcid.org/0000-0001-7436-7858
                http://orcid.org/0000-0001-6179-4404
                Article
                10.1155/2018/8941340
                6158944
                30302341
                fe24a6f9-5557-44b9-9999-25374a13a30e
                Copyright © 2018 Haiming Fang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 April 2018
                : 26 August 2018
                Funding
                Funded by: doctoral fund of the second hospital of Anhui Medical University
                Award ID: 2012BKJ004
                Funded by: clinical backbone grants of the second hospital of Anhui Medical University
                Categories
                Review Article

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