Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial

Abstract

Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.

Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.

Design, setting, and participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.

Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.

Main outcomes and measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.

Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.

Conclusions and relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.

Trial registration: anzctr.org.au Identifier: ACTRN12613000236796.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Costello reported receiving grants from the National Health and Medical Research Council and Gutsy Foundation during the conduct of the study, and fees from Janssen, Shire, Ferring, Microbiotica, and Pfizer. Dr Bryant reported receiving speaking fees from Abbvie, Shire, and Janssen; travel grant from Ferring; research grant/speaking fees from Takeda; and advisory board fees from Gilead. Dr Conlon reported receiving a grant from the National Health and Medical Research Council. Prof Roberts-Thomson reported receiving grants from the National Health and Medical Research Council and Gutsy Foundation. Dr Andrews reported receiving grants from the National Health and Medical Research Council and Gutsy Foundation during the conduct of this study and grants and/or fees from Abbott, Abbvie, Allergan, Bayer, Celgene, Gilead, Ferring, Hospira, Janssen, Merck Sharp & Dohme, Nestle, Orphan, Pfizer, Shire, Takeda, and Vifor. Prof Andrews is a Gastroenterological Society of Australia board member on Therapeutic Goods Administration–related discussions on fecal microbiota transplantation within Australia, which considers licensing, manufacture, and indications. No other disclosures were reported.

Figures

Figure 1.. Flow of Patients in Trial of Fecal Microbiota Transplantation for Ulcerative Colitis

Figure 2.. Change in Total Mayo Score for Patients

The parallel line plot shows change in Mayo score for individual patients. For each participant, a line starts at their baseline total Mayo score and finishes at their week 8 Mayo score. Boxplots of baseline and week 8 Mayo scores per treatment group present the median and interquartile range (25th to 75th percentiles) with whisker length equal to 1.5 interquartile range. aFMT indicates autologous fecal microbiota transplantation; dFMT, donor fecal microbiota transplantation.

Figure 3.. Colonic Bacterial Diversity in Patients With Ulcerative Colitis

Colonic bacterial diversity in patients with ulcerative colitis at baseline, 4 and 8 weeks after either donor fecal microbiota transplantation (dFMT) or autologous FMT (aFMT), combined groups at 12 months, and with individual donors and pooled donor stools. Diversity was assessed as the percentage of the total number of identified species.