Summary Environmental factors, mucosal permeability, and defective immunoregulation drive overactive immunity to a subset of resident gut bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutics 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 inflammatory responses . GUT-103, composed of 17 strains that synergistically provide a protective and sustained graft in the inflammatory environment of IBD, prevents and treats 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 that promote mucosal healing and immunoregulatory responses; decrease in 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 to treat and prevent relapse of IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability. |
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A new study shows how a new consortium of bacteria living in the digestive tracts of healthy individuals can be used to prevent and treat aggressive colitis in humanized mouse models.
University of North Carolina Health Care
A new study published in Nature Communications demonstrates that a consortium of bacteria engineered to complement missing or underrepresented functions in the imbalanced microbiome of patients with inflammatory bowel disease (IBD) prevented and treated immune-mediated chronic colitis in humanized mouse models.
The study’s senior author, Balfour Sartor, MD, Midget Distinguished Professor of Medicine, Microbiology and Immunology, co-director of the UNC Multidisciplinary IBD Center, said the results are encouraging for its future use in the treatment of Crohn’s disease and patients with ulcerative colitis.
| "The idea with this treatment is to restore the normal function of protective bacteria in the intestine, targeting the source of IBD, rather than treating its symptoms with traditional immunosuppressants that can cause side effects such as infections or tumors," Sartor said. . |
The live bacteria consortia, called GUT-103 and GUT-108, were developed by biotechnology firm Gusto Global. GUT-103 is made up of 17 strains of bacteria that work together to protect and feed each other. GUT-108 is a refined version of GUT-103, using 11 human isolates related to the 17 strains. These combinations allow the bacteria to remain in the colon for an extended period of time, unlike other probiotics which are not able to live in the intestine and pass through the system quickly.
GUT-103 and GUT-108 were administered orally three times a week to "germ-free" mice (with no bacteria present) that had been specially bred and treated with specific human bacteria, creating a humanized mouse model. The therapeutic bacterial consortia worked by addressing upstream targets, rather than targeting a single cytokine to block downstream inflammatory responses, and reversed established inflammation.
"It also decreased pathobionts, bacteria that can cause damage, while expanding resident protective bacteria and producing metabolites that promote mucosal healing and immunoregulatory responses," Sartor said. "Simply put, the treatment increased the good guys and decreased the bad guys."
Due to the strong results seen in this study and the need for more alternative therapies for Crohn’s disease, Sartor would like to see GUT-103 and GUT-108 studied in Phase 1 and 2 clinical trials in the future. He plans to continue his work with Gusto Global to further explore the uses of bacterial consortia.
