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.

This project was funded by Microba Life Sciences. Johanna K. Ljungberg, Joyce Zhou, Michael Nissen, Annika Krueger, Joel Boyd, Mareike Bongers, Jimenez Loayza Jeimy, Charlotte Vivian, Andrea Rabellino, Rhys Newell, Liang Fang, Samantha MacDonald, Alena Pribyl, Luke Reid, Nicola Angel, David L.A. Wood, Blake Wills, Trent Munro, Paraic O Cuiv, Lutz Krause are or have been employees of Microba Life Sciences. Ella Reich completed an industry at Microba Life Sciences. Gene W. Tyson and Philip Hugenholtz are the founders of Microba Life Sciences. Shandelle Caban, Huw McCarthy, Joanne Soh, Simon Keely and Hiram Chipperfield have provided paid services to Microba Life Sciences. Ian H. Frazer is non-executive director and both he and Jakob Begun are members of the medical advisory board at Microba Life Sciences. Microba Life Sciences is a microbial genomics company developing microbiome-based diagnostic tests and therapeutics.

ACTRN12623000291684

This project was funded by Microba Life Sciences.

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The ethics committee of Bellberry Limited and the Alfred Health Human Research Ethics Committee gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors