Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease

Byron P. Vaughn, Tommi Vatanen, Jessica R. Allegretti, Aiping Bai, Ramnik J. Xavier, Joshua Korzenik, Dirk Gevers, Amanda Ting, Simon C. Robson, Alan C. Moss

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Background: The microbiota in the lumen of patients with Crohn's disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to fecal microbial transplantation (FMT) from healthy individuals to subjects with active CD. Methods: We performed a prospective open-label study (uncontrolled) of FMT from healthy donors to subjects with active CD. A single FMT was performed by colonoscopy. Recipients' microbial diversity, mucosal T-cell phenotypes, and clinical and inflammatory parameters were measured over 12 weeks, and safety over 26 weeks. Results: Nineteen subjects were treated with FMT and completed the study follow-up. Fifty-eight percent (11/19) demonstrated a clinical response (Harvey-Bradshaw Index decrease >3) following FMT. Fifteen subjects had sufficient pre/postfecal samples for analysis. A significant increase in microbial diversity occurred after FMT (P = 0.02). This was greater in clinical responders than nonresponders. Patients who experienced a clinical response demonstrated a significant shift in fecal microbial composition toward their donor's profile as assessed by the Bray-Curtis index at 4 weeks (P = 0.003). An increase in regulatory T cells (CD4+CD25+CD127lo) was also noted in recipients' lamina propria following FMT. No serious adverse events were noted over the 26-week study period. Conclusions: In this open-label study, FMT led to an expansion in microbial bacterial diversity in patients with active CD. FMT was overall safe, although the clinical response was variable. Determining donor microbial factors that influence clinical response is needed before randomized clinical trials of FMT in CD.

Original languageEnglish (US)
Pages (from-to)2182-2190
Number of pages9
JournalInflammatory bowel diseases
Volume22
Issue number9
DOIs
StatePublished - Aug 10 2016

Bibliographical note

Funding Information:
Project support from grant to the Harvard Institute of Translational Immunology (HITI) from the Leona and Harry Helmsley Charitable Trust (A.C.M.). A. C. Moss is supported by NIH grant K23DK084338. B. P. Vaughn is supported by NIH grant 5T32DK007760-14.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Clinical Trials
  • microbiology of IBD
  • rohn's disease

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