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Evaluating microbial determinants of donor efficacy to translate faecal microbiota transplantation from research to clinical practice

After becoming an established therapy for recurrent Clostridioides difficile infection (rCDI), faecal microbiota transplantation (FMT) has been investigated also in non-communicable disorders, including IBD, IBS, metabolic syndrome, neurological disease and others. 1 While the transfer of a healthy biomass appears to be effective regardless of its composition in rCDI (which is an example of acute, elementary dysbiosis), increasing evidence suggests that the clinical success of FMT in chronic disorders is influenced by several factors, including donor microbiome composition 2 or FMT working protocols, 3 and that these effects may be mediated by the engraftment capacity of the donor microbiome into the recipient gut. 4 Haifer et al 5 have published in the latest issue of Gut a subanalysis of a recent randomised trial (the LOTUS trial) of FMT for UC, 6 where they had observed a significant variability of clinical efficacy between the two recruited donors (100% vs 36%). They have determined the differ-ences in donor microbiome profiles by whole genome sequencing and untargeted metabolomics, validating results in another independent cohort, with a series of major findings. 5 First, donors and patients with UC differed significantly in the composition and function of gut microbiota, in line with previous experiences. More strikingly, the stability in richness of donor species over time (assessed for up to 70 weeks), rather than richness itself, was associated with therapeutic efficacy. Along with this result, evenness of donor species was associated with higher donor engraftment as well as with clinical response, and the stability of less effective donor appeared to be influenced by Prevotella copri . Finally, the two donors differed in terms of taxonomic and functional char-acteristics of gut microbiome, as