A human microbiome-derived therapeutic for ulcerative colitis promotes mucosal healing and immune homeostasis: a randomized, controlled Phase 1 trial in healthy volunteers

Using a metagenome-guided, large cohort-based approach, we identified Hominenteromicrobium mulieris as prevalent in healthy individuals but depleted in ulcerative colitis. In murine colitis models, a newly isolated strain of this species, MH27-2, improved disease pathology and accelerated gut healing, marked by epithelial restitution and reduced immune cell infiltration. In vitro, MH27-2 promoted mucosal healing, through accelerating epithelial cell migration and proliferation, and by improving gut barrier integrity and supporting immune homeostasis. Scalable manufacturing processes were developed and the safety of MH27-2 drug product, MAP 315, was evaluated in a randomized, double-blind, placebo-controlled, multiple-dose Phase 1 trial (ACTRN12623000291684). MAP 315 or placebo was administered daily for 14 days to 32 healthy female and male adults. MAP 315 was safe and well-tolerated, with no serious adverse events, bacterial translocation, or clinically significant changes in inflammatory markers, supporting its further clinical development as a novel microbiome-derived therapeutic for ulcerative colitis.