A human microbiome-derived therapeutic for ulcerative colitis promotes mucosal healing and immune homeostasis
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The gut microbiome is central to the pathogenesis of ulcerative colitis (UC), and microbiome-derived therapeutics are a promising new treatment option. Using a metagenome-guided, large cohort-based approach, we identified Hominenteromicrobium mulieris as prevalent in healthy individuals but depleted in UC. Here, we present a Live Biotherapeutic Product (LBP) candidate, MAP 315, derived from a newly isolated strain of this species (MH27-2). In mouse colitis models, MH27-2 improved disease pathology, and accelerated gut healing, marked by epithelial restitution and reduced immune cell infiltration. In vitro studies showed that MH27-2 promotes mucosal healing through accelerated epithelial cell migration and proliferation, accelerated wound closure, and improved gut barrier integrity. Importantly, MH27-2 supports immune homeostasis through the promotion of regulatory T-cells, suppression of TL1A signaling, and induction of anti-inflammatory IL-10. Manufacturing processes were developed, and MH27-2 drug product (MAP 315) demonstrated to be safe and well-tolerated in a first-in-human Phase 1 clinical trial.
