Daniel van der Lelie, Akihiko Oka, Safiyh Taghavi, Junji Umeno, Ting-Jia Fan, Katherine E Merrell, Sarah D Watson, Lisa Ouellette, Bo Liu, Muyiwa Awoniyi, Yunjia Lai, Liang Chi, Kun Lu, Christopher S Henry, R Balfour Sartor
Nature communications 2021 May 28Environmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability.
Daniel van der Lelie, Akihiko Oka, Safiyh Taghavi, Junji Umeno, Ting-Jia Fan, Katherine E Merrell, Sarah D Watson, Lisa Ouellette, Bo Liu, Muyiwa Awoniyi, Yunjia Lai, Liang Chi, Kun Lu, Christopher S Henry, R Balfour Sartor. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nature communications. 2021 May 28;12(1):3105
PMID: 34050144
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