PR002421 (Project)

Description:Background Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) supports clinical response and deep remission in patients with active ulcerative colitis (UC). The present study aims to assess FMT-associated bacterial, fungal and metabolomic shifts in mucosal and faecal niches in active UC, and to correlate these changes with clinical and endoscopic outcomes of FMT. Study also determines if baseline microbial signatures in UC can determine FMT engraftment and clinical outcomes. We performed a prospective cohort study of patients with UC, recruited as part of the FMT-AID trial, and randomised to receive either 8-week FMT-AID or standard medical therapy (SMT). Non-IBD controls were also recruited in the study. Faecal and mucosal microbiome and mycobiome were characterised in 104 paired pre- and post-intervention samples (n=52, faecal; n=52, mucosal) from 26 patients (16 in FMT-AID arm + 10 in SMT arm) In addition, 48 non-IBD control samples (n=21, faecal; n=27, mucosal) were collected at single time point from 27 subjects. Clinical response (reduction in SCCAI≥3) was the primary outcome. A subset of samples (n=71; 40 paired pre-and post-FMT samples and 31 non-IBD control samples) were used for untargeted metabolomics. Results FMT-AID remodelled mucosal (β-diversity-adonis R2=2.13, p=0.02) and faecal (R2=2.76, p=0.003) bacterial communities and enhanced faecal bacterial diversity (p<0.001). FMT-AID enriched the gut with beneficial bacterial taxa (mucosal-Odoribacter and faecal- Slackia, Agathobaculum and Aldercreutzia) and reduced pathobiont abundances (mucosal- Enterococcus, Veillonella, Malassezia; faecal- Enterococcus, Candida tropicalis). Compared to clinical responders to FMT-AID, the non-responders had a distinct gut microbiome signature, which associated with elevated disease activity (Megasphaera and UCEIS (R=0.77, FDR-q=0.02), Malassezia slooffiae and SCCAI (R=0.81; FDR-q=0.01), UCEIS (R=0.62; FDR-q=0.12) and FCP (R=0.88; FDR-q=0.003)]. FMT-AID also restored mucosal and faecal metabolome with ‘health-associated’ metabolites. Higher pre-intervention abundances of beneficial taxa in mucosa and faeces associated with positive outcomes of FMT-AID. Pre-FMT faecal bacteriome also correlated with post-FMT engraftment of beneficial bacteria. Conclusions Enrichment of specific beneficial bacterial, fungal and metabolomic signatures in faecal and mucosal niches was associated with positive clinical, biochemical and endoscopic outcomes following FMT-AID in patients with UC. Pre-FMT bacteriome was associated with post-FMT engraftment of beneficial bacteria and clinical response.