RESEARCH TRIANGLE PARK – Healthy microbiome developed by a Triangle biotech startup that targets inflammatory diseases shows promise as a “breakthrough” therapy.

Gusto Global, a microbiome discovery platform company focused on restoring a healthy microbiome, has developed novel consortia of bacteria for treating Crohn’s disease and ulcerative colitis in patients.

A new study published this month in Nature Communications this month by the startup and top UNC-Chapel Hill scientists demonstrated that the live bacterial consortia, called GUT-103 and GUT-108, prevented and treated chronic immune-mediated colitis in humanized mouse models.

“Best-in-class preclinical results for a Live Biotherapeutic Product validate Gusto’s bottom-up rational consortium design approach that is rigorously informed by mechanistic modeling and insights from microbiome ecology and disease pathogenesis,” said Dr. Daniel van der Lelie, Gusto Global’s CEO.

Crohn’s disease and ulcerative colitis are both forms of inflammatory bowel diseases (IBD). They affect at least 1.6 million Americans, most of whom are diagnosed before age 30. These chronic, life-long conditions can be treated but not cured.

“This design of the optimal microbiome restoration therapy takes sharp aim at root causes and is a significant breakthrough for the microbiome field which lacks mechanistic understanding,” van der Lelie said.

GUT-103 is comprised 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 permit the bacteria to stay in the colon for an extended amount of time, as opposed to other probiotics that are not capable of living in the gut and pass through the system quickly.

In the study conducted at UNC-Chapel Hill and funded by Global Gusto, GUT-103 and GUT-108 were given orally three times a week to “germ-free” mice (no bacteria present) that were colonized either by specific human bacteria, or a fecal transplant from a healthy donor, to create a “humanized” mouse model of moderate to severe colitis.

“The idea of this treatment is to restore the normal function of the protective intestinal bacteria by targeting the underlying cause of IBD, instead of treating its symptoms with traditional immunosuppressants that can cause side effects like infections or tumors,” said a senior author, Balfour Sartor, MD, Midget Distinguished Professor of Medicine, Microbiology and Immunology, Co-Director of the UNC Center for Gastrointestinal Biology and Disease.

“It also decreased pathobionts — bacteria that can cause harm — while expanding resident protective bacteria, and produced metabolites promoting mucosal healing and immunoregulatory responses,” Sartor added.

GUT-108 is expected to advance into Phase 1 clinical trial.

Founded in 2016, Gusto Global is pioneering the world’s first digital map of host-microbiome ecological interactions.

Its proprietary GUST+ bioinformatics, computational modeling and predictive analytics platform uses advanced metagenomics-based analysis to interpret dynamic molecular communication, both within microbial communities and in their mechanistic interface with human systems.