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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis.

Authors: van der Lelie, Daniel; Oka, Akihiko; Taghavi, Safiyh; Umeno, Junji; Fan, Ting-Jia; Merrell, Katherine E; Watson, Sarah D; Ouellette, Lisa; Liu, Bo; Awoniyi, Muyiwa; Lai, Yunjia; Chi, Liang; Lu, Kun; Henry, Christopher S; Sartor, R Balfour

Published In Nat Commun, (2021 05 28)

Abstract: Environmental 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.

PubMed ID: 34050144 Exiting the NIEHS site

MeSH Terms: Animals; Bacteria/genetics; Bacteria/metabolism*; Bile Acids and Salts/metabolism; Colitis/immunology; Colitis/microbiology*; Colitis/therapy*; Cytokines/metabolism*; Disease Models, Animal; Dysbiosis/microbiology*; Dysbiosis/therapy; Feces/microbiology; Gastrointestinal Microbiome*/immunology; Gastrointestinal Microbiome*/physiology; Germ-Free Life*/immunology; Germ-Free Life*/physiology; Homeostasis; Humans; Inflammation/metabolism; Intestinal Mucosa/metabolism; Intestinal Mucosa/microbiology; Metabolomics; Mice; Mice, Inbred C57BL; Mice, Knockout

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