A human microbiome-derived therapeutic for ulcerative colitis promotes mucosal healing and immune homeostasis
O Cuiv, P.; Ljungberg, J.; Zhou, J.; Nissen, M.; Krueger, A.; Boyd, J.; Bongers, M.; Jimenez Loayza, J.; Vivian, C.; Reich, E.; Rabellino, A.; Newell, R.; Fang, L.; MacDonald, S.; Pribyl, A.; Caban, S.; McCarthy, H.; Soh, J.; Reid, L.; Wills, B.; McHale, D.; Wood, D.; Frazer, I.; Angel, N.; Chipperfield, H.; Begun, J.; Keely, S.; Tyson, G.; Hugenholtz, P.; Munro, T.; Krause, L.
Show abstract
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.
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