Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis

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 Յ2 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.

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study)

“…Although FMT seems to be a viable option for treatment of UC in future, [1][2][3][4][5] and is being propagated as "natural" therapy, its safety over short term, and more importantly over long term needs to be studied. With FMT, there are risks about unfavorable effects that donor microbiota may have on recipients.…”

“…Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is emerging as a novel therapy for ulcerative colitis (UC). The efficacy of FMT in induction of remission in moderate-severe active UC has been addressed by four highquality randomized controlled trials [1][2][3][4] and multiple cohort studies. FMT has been shown to be effective in patients with steroiddependent UC, 5,6 and it may also have a role in long-term maintenance of remission.…”

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

“…Unlike the effect of microflora transplantation on recurrent CDI, the results of many studies on FMT in UC are heterogeneous [123][124][125][126][127][128][129][130][131][132] owing to the lack of a standardized process ( Table 2). 9 One study suggests that the microbial imbalance of the CDI + UC recipients is similar to that of CDI-only recipients 140 Thus, the efficacy for FMT treatment in UC is probably attributed to the occurrence of bacterial dysregulation similar to that seen in CDI.…”

Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas

“…FMT is effective for treating recurrent Clostridioides difficile infection (rCDI) (van Nood et al 2013), but is also under investigation for the treatment of ulcerative colitis (UC), Crohn's disease (CD), liver diseases, obesity and metabolic disease, food allergy, graft-versus-host disease, check point colitis and to improve the efficacy of cancer immunotherapy (Ooijevaar et al 2019;Wang et al 2018;Baruch et al 2019). Clinical trials of FMT in UC have suggested some potential for using microbiota-targeted therapy in this setting (Paramsothy et al 2017;Moayyedi et al 2015;Rossen et al 2015;Costello et al 2019), but evidence for efficacy in other indications is currently extremely limited and there is currently little or no scientific basis for the adoption of FMT as a mainstream therapeutic option outside of rCDI.…”