Our HAHSO-funded research program was the first multicentre placebo-controlled trial of fecal microbiota transplant (FMT) for pediatric ulcerative colitis. We offered the strongest published data showing that FMT can improve clinical symptoms and underlying mucosal inflammation in pediatric ulcerative colitis patients, and that these benefits may last for up to 6 months after treatment. We conducted our trial across two Ontario, and one Quebec pediatric academic health sciences centres showing that this treatment can be successfully implemented across different institutions. While FMT is still tremendously nascent in pediatrics across Canada, our trial has helped establish a robust infrastructure for future pediatric FMT research and clinical FMT therapy across Ontario. Our research has led to developing the first dedicated pediatric FMT stool bank in Ontario, and follow-on trials in pediatric Crohn’s disease (completed), anorexia nervosa and bacterial overgrowth (planned).

In 2015, our team conducted the first multi-centre pilot trial of fecal microbiota transplant (FMT) in pediatric ulcerative colitis (UC). Our OBJECTIVES were to demonstrate clinical efficacy and feasibility of administering a 6-week treatment of FMT enemas to children with active UC.

Our METHODS involved using healthy, screened FMT materials to administer 12 enema-based treatments over 6-weeks across three pediatric centres. Participants were randomized to active (FMT) or placebo treatments (dyed normal saline) and allowed to remain on existing treatments during the intervention.

Our RESULTS showed that of 48 patients referred to our study, 25 patients were randomized to FMT (n=13) or placebo (n=12) arms. 92% (11 of 12) FMT recipients reached the composite clinical endpoint (improvement in clinical disease activity or inflammatory markers) in the FMT group (week 6), vs. 50% (6 of 12) in the placebo group (RR 1.8, 95% CI: 1.1-3.7). 75% (9 of 12) maintained clinical response at 12 months. In our open-label placebo crossover extension, 84% (16 of 19) FMT recipients reached the composite endpoint at week 6. Microbial taxa associated with improvement included Alistipes and Escherichia spp. A non-significant increase in adverse events was found in FMT recipients.

In CONCLUSION, our trial offered the first RCT evidence that FMT has a therapeutic role in pediatric UC disease activity, and that long-term response may persist after final FMT infusion. We did not achieve recruitment targets and we explored these CHALLENGES through a qualitative follow-up study of participants. Our intensive treatment protocol was cited as a factor.

Our data suggests patients/families are highly interested in microbiota-based treatments. NEXT STEPS have included completing a second, follow-on study of FMT in pediatric Crohn’s disease. These results, and further studies of FMT across pediatric UC and other indications are ongoing.

Pai N, Popov J, Hill L, Hartung E, Grzywacz K, Moayyedi P; McMaster Pediatric Fecal Microbiota Transplant Research Collaboration. Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects. Gastroenterology. 2021 Aug;161(2):388-393.e3. doi: 10.1053/j.gastro.2021.04.067.

Popov J, Caputi V, Nandeesha N, Rodriguez DA, Pai N. Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies. Int J Mol Sci. 2021 Oct 21;22(21):11365. doi: 10.3390/ijms222111365.

Popov J, Hartung E, Hill L, Chauhan U, Pai N. Pediatric Patient and Parent Perceptions of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis. J Pediatr Gastroenterol Nutr. 2021 Dec 1;73(6):684-688. doi: 10.1097/MPG.0000000000002995.

Pai N, Popov J, Hill L, Hartung E. Protocol for a double-blind, randomised, placebo-controlled pilot study for assessing the feasibility and efficacy of faecal microbiota transplant in a paediatric Crohn’s disease population: PediCRaFT Trial. BMJ Open. 2019 Nov 28;9(11):e030120. doi: 10.1136/bmjopen-2019-030120.

Pai N, Popov J. Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial. BMJ Open. 2017 Aug 21;7(8):e016698. doi: 10.1136/bmjopen-2017-016698.