Abstract
Background & Aims Recurrent and refractory Clostridium difficile infections (CDI) are effectively treated with fecal microbiota transplant (FMT). Uncertainty exists regarding the effectiveness of FMT for CDI with underlying inflammatory bowel disease (IBD), its effects on disease activity and its effectiveness transferring the donor microbiome to patients with and without IBD. This study aims to determine FMTs effectiveness in subjects with and without IBD, its impact on IBD activity, the level of microbiome engraftment, and predictors of CDI recurrence.
Methods Subjects with and without IBD who underwent FMT for recurrent or refractory CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) Frequency of IBD flare after FMT; (3) Microbiome engraftment after FMT; (4) Predictors of CDI recurrence.
Results Overall, 134 patients, 46 with IBD, were treated with FMT. There was no difference in recurrence in patients with and without IBD at 2 months (22.5% vs 17.9%; p=0.63) and 6 months (38.7% vs 36.5%; p>0.99). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. The pre-FMT microbiome was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment. There was no difference in engraftment based on IBD endoscopic severity at FMT.
Conclusions IBD did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiome was not predictive of recurrence, and microbial engraftment was dependent on IBD treatment escalation but not on underlying disease severity.
Author Contributions: Conception and design: RPH, AG, SCF, JCC. Generation, collection, assembly, analysis, and/or interpretation of the data: RPH, AG, SCF, JCC, LY, MSF, JR, EJC, IM, NY, TL, PL, JJF. Drafting or revision of the manuscript: RPH, AG, SCF, LY, MSF, JR, EJC, IM, NY, TL, PRL, IP, JHC, BES, JFC, JJF, JCC. Approval of the final version of the manuscript: All authors read, reviewed, and approved the final version of the manuscript.
Footnotes
↵* Robert P Hirten, Ari Grinspan, Shih-Chen Fu should be considered joint first authors
Grant Support: This study was funded in part by the SUCCESS (Sinai Ulcerative Colitis Clinical, Experimental and System Studies) grant from the Bacchetta Foundation (SCF, IP, JHC, JFC, JJF, JCC), the Crohn’s and Colitis Foundation of America grant #362048 (JJF, JCC), and the George Waechter Memorial Foundation grant (AG).
Abbreviations
- Anti-TNF
- anti-tumor necrosis factor
- AZA
- azathioprine
- BMI
- body mass index
- CD
- crohn’s disease
- CDI
- clostridium difficile infection
- CDIR
- clostridium difficile infection relapse
- CRP
- c-reactive protein
- ESR
- erythrocyte sedimentation rate
- FMT
- fecal microbiota transplant
- GERD
- gastroesophageal reflux disease
- HBI
- Harvey Bradshaw Index
- IBD
- inflammatory bowel disease
- Non-IBD
- non-inflammatory bowel disease group
- IBDe
- inflammatory bowel disease medication escalation
- IBDs
- inflammatory bowel disease no medication escalation
- J tube
- jejunal tube
- LSM
- least-squares means
- MP
- mercaptopurine
- MTX
- methotrexate
- OTUs
- operational Taxonomic Units
- PCoA
- principal coordinate analysis
- PEG
- percutaneous endoscopic gastrostomy
- PPI
- proton pump inhibitor
- PUD
- peptic ulcer disease
- SD
- standard deviation
- SES-CD
- simple endoscopic score for Crohn’s disease
- UC
- ulcerative colitis
- WBC
- white blood cell count
Writing Assistance: No writing assistance was provided to the authors.
Disclosures: RPH served as a consultant, advisory board member or speaker for Janssen and Takeda.
JFC has served as consultant, advisory board member or speaker for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Lilly, Medimmune, Merck & Co., Pfizer, PPM Services, Protagonist, Second Genome, Seres, Shire, Takeda, Theradiag, Theravance Biopharma. Speaker for AbbVie, Ferring, Pfizer, Takeda, Shire. Stock options: Intestinal Biotech Development, Genfit. Research Grants: AbbVie, Takeda, Janssen and Janssen
JJF has served as consultant, advisory board member or speaker for Vedanta Biosciences and Janssen. Research Grants: Janssen
BES has received consulting fees and research grants from AbbVie, Pfizer, Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda, and has received consulting fees from Boehringer Ingelheim, Akros Pharma, Arena Pharmaceuticals, Forward Pharma, Immune Pharmaceuticals, Lilly, Synergy Pharmaceuticals, Theravance, Receptos, TiGenix, TopiVert Pharma, MedImmune, Vedanta Biosciences, Allergan, UCB Pharma, EnGene, Target PharmaSolutions, Lycer, Lyndra, Vivelix Pharmaceuticals, Oppilan Pharma, and Gilead
JHC serves as a consultant for Pfizer and has a sponsored research agreement with Goldfinch Bio.
All other authors declare no conflict of interest.