Drivers and determinants of strain dynamics following fecal microbiota transplantation

TLDR

Fecal microbiota transplantation is used to treat inflammatory gastrointestinal diseases, yet its clinical mechanisms and resulting microbiome changes remain poorly understood. We profiled 316 pre‑ and post‑FMT metagenomes across ten indications, quantifying strain‑level dynamics of 1,089 species and assembling 47,548 new genomes. Donor strain colonization and recipient strain resilience were largely independent of clinical outcomes but could be accurately predicted with LASSO models incorporating host, microbiome, and procedural variables, highlighting donor–recipient complementarity as the key determinant and offering ecological parameters to guide more effective, patient‑stratified microbiome therapies.

Abstract

Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor–recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.