Colon to Rectum
Lancet Gastroenterol Hepatol. 2022;7(2):141–51
Lyophilized oral fecal microbiota transplantation for ulcerative colitis (LOTUS): A randomized, double-blind, placebo-controlled trial
Background: Fecal microbiota transplantation (FMT) delivered via colonoscopic infusion or enemas have been shown to induce remission in a proportion of patients with active ulcerative colitis. Whether orally administered FMT is effective in ulcerative colitis is unknown. The aim of this trial was to assess the efficacy of oral lyophilized FMT for the treatment of active ulcerative colitis.
Methods: A double-blind, randomized, placebo-controlled trial was conducted at 2 centers in Australia. Eligible patients were aged 18–75 years with active ulcerative colitis (defined as clinical and endoscopic active ulcerative colitis, with a total Mayo score of 4–10, and a Mayo endoscopic subscore ≥ 1). After 2 weeks of amoxicillin, metronidazole, and doxycycline, patients were randomly assigned in a 1:1 ratio to receive either oral lyophilized FMT or placebo capsules for 8 weeks, using a prespecified computer-generated randomization list with a permuted block size of 8. The primary outcome was corticosteroid-free clinical remission with endoscopic remission or response (total Mayo score ≤ 2, all subscores ≤ 1, and ≥ 1-point reduction in endoscopic subscore) at week 8. At week 8, FMT responders were randomly assigned (in a 1:1 ratio, permuted block size of 8) to either continue or withdraw FMT for a further 48 weeks. Analyses were done by modified intention-to-treat, including all patients who received at least 1 study dose.
Findings: Between May 20, 2019, and March 24, 2020, 35 patients were randomly assigned: 15 to receive FMT and 20 to receive placebo. Recruitment was terminated early due to the COVID-19 pandemic. At week 8, 8 of 15 patients (53%) in the FMT group were in corticosteroid-free clinical remission with endoscopic remission or response, as were 3 of 20 patients (15%) in the placebo group (difference 38.3%, 95% confidence interval [CI]: 8.6–68.0; p = 0.027; odds ratio = 5.0, 95% CI: 1.8–14.1). Adverse events occurred in 10 patients (67%) in the FMT group and 17 (85%) of those in the placebo group during the 8-week induction period, and were generally mild and self-limiting gastrointestinal complaints. Serious adverse events included worsening ulcerative colitis (2 in the FMT group, 1 in the placebo group) and per-rectal bleeding (1 in the placebo group). Ten patients in the FMT group who achieved a clinical or endoscopic response entered the maintenance phase and were randomly assigned to continue open-label FMT (n = 4) or withdraw therapy (n = 6). All 4 patients (100%) who continued FMT were in clinical, endoscopic, and histologic remission at week 56 compared with none of the patients who had FMT withdrawn.
Interpretation: Antibiotics followed by orally administered fecal microbiota transplantation (FMT) was associated with the induction of remission in patients with active ulcerative colitis. Continuing FMT was well tolerated and appeared to demonstrate clinical, endoscopic, and histological efficacy. Oral FMT could be a promising and feasible treatment option for patients with ulcerative colitis.