Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection

Abstract

Background: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.

Methods: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.

Results: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04).

Conclusion: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.

Keywords: Clostridioides difficile infection; Crohn’s disease; butyrate; fecal microbiota transplantation; inflammatory bowel disease; microbiome; ulcerative colitis.

FIGURE 1.

Alpha diversity after (A) first FMT and (B) in patients receiving second FMT. Increases were significant after first FMT for all patients pooled (P < 1e-17) and when stratified by IBD subtype (UC P < 1e-13; CD P < 1e-5).

FIGURE 2.

Similarity to the donor post-FMT measured by Jensen-Shannon Divergence, stratified by donor and IBD subtype. Data from 2 patients receiving other donors not shown. Change was measured as difference in similarity post-FMT vs baseline and was significantly different between UC and CD patients (all patients, P = 0.040; donor 1 and 2 only, P = 0.038, 2-sided t test). Differences between the subtypes were largest among recipients of donor 2.

FIGURE 3.

Log fold-change in primary and secondary bile acids following FMT. For each patient, all values post-FMT were averaged, then divided by the patient’s baseline. Significant changes are indicated (*indicates P < 0.05, **indicates P < 0.005, 2-sided t test on log abundance).

FIGURE 4.

Associations between changes in fecal butyrate and major phyla abundances. Changes were measured between baseline and week 12 for 2 major phyla: Firmicutes (left) and Proteobacteria (right). Spearman correlations were significant for Firmicutes across all patients (P = 0.021) and when stratified by IBD subtype (UC, P = 0.037; CD, P = 0.039).