Microbial determinants of effective donors in faecal microbiota transplantation for UC.

Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection. Faecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomics RESULTS: Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (≥75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics. Donor microbiota stability and species evenness were identified as novel metrics that were 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. ACTRN12619000611123.

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Déclaration de conflit d'intérêts

Competing interests: CH reports speaker fees and educational support from Janssen, Pfizer, Takeda, Ferring, Sandoz and Abbvie. SP has served as a consultant for Finch Therapeutics and has received speaker fees from Ferring, Janssen and Takeda. TJB has a pecuniary interest in the Centre for Digestive Diseases, is a medical advisor to Finch Therapeutics, RedHill Bio and Topelia Aust, and holds patents in FMT treatment. RWL reports personal fees from AbbVie, Aspen, Ferring, Celgene, Dr Falk Pharma, Novartis, MSD, Chiesi, BMS and Glutagen; grants and personal fees from Hospira/Pfizer, Janssen and Takeda; grants from Shire Dr Falk Pharma, outside the submitted work. All other authors have no conflicts of interest to declare.