Faecal microbiota transplantation (FMT) is traditionally delivered via colonoscopic infusion or enemas and have been shown to induce remission in a proportion of patients with active ulcerative colitis (UC). However, it is unknown whether orally administered FMT is effective in inducing remission. We conducted a double-blind, randomised controlled trial to assess the efficacy of single-donor lyophilised oral FMT for the treatment of active UC (LOTUS).
Faecal samples from the two healthy donors were collected over 44 (donor 1) or 70 (donor 2) weeks and used to prepare lyophilised FMT. Thirty-five UC patients received 2 weeks of antibiotics followed by random assignment to receive FMT (n=15) or placebo (n=20). At week 8, eight (53%) of 15 patients in the FMT group were in remission compared to three (15%) of 20 in the placebo group (difference 38.3%, 95% CI 8.6–68.0; p=0·027; odds ratio 5.0, 95% CI 1.8–14.1).
Interestingly, a significant donor effect was observed. One donor had 100% efficacy at inducing remission (4/4 patients) whereas the second donor’s efficacy was 36% (4/11 patients). Shotgun metagnomics and metabolomics were performed on donor faecal samples to identify taxonomic and functional differences within the gut microbiota of both donors in order to improve future donor selection.
Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy and led to increased donor species engraftment in patients. 90 bacterial species and one archaeon were differentially abundant between donors including Methanobrevibacter smithi, Ruminococcus bromii, Eubacterium halii etc. Taxonomic differences between donors translated to microbial functional differences that were validated using metabolomics including differences in dipeptides, polypeptides and metabolites involved with bile and benzoate metabolism.
This work demonstrated that antibiotics followed by oral FMT was associated with remission and could be a promising and feasible treatment option for UC. Donor microbiota stability and species evenness were identified as novel metrics associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host and can be used to inform rational FMT donor selection.