New consortium of bacteria can be used to treat aggressive colitis in humanized mouse models

A new study reported in Nature Communications shows that a consortium of bacteria, developed to complement lacking or poorly represented functions in the imbalanced microbiome of inflammatory bowel disease (IBD) patients, inhibited and treated chronic immune-mediated colitis in humanized mouse models.  

New consortium of bacteria can be used to treat aggressive colitis in humanized mouse models
Balfour Sartor, MD. Image Credit: University of North Carolina Health Care.

Balfour Sartor, MD, senior author of the study, Midget Distinguished Professor of Medicine, Microbiology and Immunology, and Co-Director of the UNC Multidisciplinary IBD Center, stated that the findings are promising for future use in treating patients with ulcerative colitis and Crohn’s disease.

The idea with this treatment is to restore the normal function of the protective bacteria in the gut, targeting the source of IBD, instead of treating its symptoms with traditional immunosuppressants that can cause side effects like infections or tumors.”

Balfour Sartor, MD, Study Senior Author and Midget Distinguished Professor of Medicine, Microbiology and Immunology, University of North Carolina Health Care

The live bacteria consortia, also known as GUT-103 and GUT-108, were developed by Gusto Global, a biotech firm. GUT-103 consists of 17 strains of bacteria that work collaboratively to safeguard and feed each other.

GUT-108 is an improved version of GUT-103 made using 11 human isolates connected to the 17 strains. Such combinations allow the bacteria to remain in the colon for a very long time, as against other probiotics that cannot survive in the gut and pass via the system rapidly.

Oral administration of GUT-103 and GUT-108 three times per week was carried out to “germ-free” mice (no existence of bacteria) that had been particularly developed and treated with specific human bacteria, thereby making a humanized mouse model.

The therapeutic bacteria consortia functioned by meeting the upstream targets, instead of aiming at a single cytokine to stop downstream inflammation responses, and inverted established inflammation.

It also decreased pathobionts—bacteria that can cause harm—while expanding resident protective bacteria, and produced metabolites promoting mucosal healing and immunoregulatory responses. Simply put—the treatment increased the good guys and decreased the bad guys.”

Balfour Sartor, MD, Study Senior Author and Midget Distinguished Professor of Medicine, Microbiology, and Immunology, University of North Carolina Health Care

As a result of the strong findings observed in this study, and the requirement for more alternative therapies for Crohn’s disease, Sartor would like to have GUT-103 and GUT-108 studied in Phase 1 and 2 clinical trials ahead. He plans to proceed with his work with Gusto Global to additionally examine the uses of the bacterial consortia.

This work was financially supported by Gusto Global, LLC. Daniel Van der Lelie, PhD, Chief Executive Officer of Gusto Global, is the first author of this study. Germ-free mice were offered by grants from the National Institutes of Health (NIH) and the Crohn’s and Colitis Foundation.

Source:
Journal reference:

Van der Lelie, D., et al. (2021) Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nature Communications. doi.org/10.1038/s41467-021-23460-x.

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