MH002, a Novel Butyrate-Producing Consortium of Six Commensal Bacterial Strains Has Immune-Modulatory and...

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition of the gastrointestinal tract. It is generally accepted that IBD is characterized by an inappropriate immune response to the intestinal microbiome in genetically susceptible individuals. Despite the available treatment options ranging from salicylates and corticosteroids, to immunosuppressants and biologics, there is still a high unmet medical need for patients who respond poorly to drugs or are not able to tolerate them. Microbiome-based therapeutics offer a valid treatment strategy for IBD with enhanced safety. A butyrate-producing consortium of six commensal strains (MH002) was evaluated in a series of in vitro, ex vivo, and in vivo experiments mimicking multiple IBD-related dysfunctions, namely disrupted intestinal permeability and immune activation. MH002 rapidly produced high levels of butyrate in fed-batch cultures, and significantly increased butyrate levels within one day after administration to IBD-derived gut microbial communities in vitro. Both in Caco-2/peripheral blood mononuclear cells (PBMCs) co-cultures, and IBD patients-derived organoids and colonic explants, MH002 reduced inflammation and restored epithelial barrier integrity. In addition, MH002 promoted wound repair in vitro. Finally, MH002 protected mice and rats from chemically induced colitis. Altogether, results showed that MH002 presents a novel therapeutic avenue for the treatment of IBD.