05/17/2021
Targeting the Gut Microbiome to Treat or Prevent Inflammatory Bowel Disease
Phillip Ahern, DPhil, has been awarded a five-year, $2.3 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, to identify new strategies to advance the efficacy of probiotics for the treatment of inflammatory bowel disease (IBD).
Maintaining homeostasis between intestinal immune cells and gut microbiota (the microbes and viruses that inhabit the intestines) is a key factor in host health and dependent on maintaining a balance between pro- and anti-inflammatory pathways. Disrupting this balance can trigger chronic inflammation in the gastrointestinal tract, which can result in the onset of IBD—an increasingly prevalent condition that now affects more than one percent of adults in the United States.
Probiotic therapies provide opportunities for enhanced treatment
To date, most IBD therapies under development target pathogenic inflammatory immune factors and pathways. However, this approach can suppress patients’ immune response and enhance susceptibility to infection, underscoring the need for new treatment strategies that improve outcomes without increasing risk for infections.
With this new grant, the Ahern team will turn their attention to gut microbes, which research shows have evolved strategies to modulate the host immune system, and how microbial pathways may instead be targeted to treat IBD.
Tracing B. thetaiotaomicron in gastrointestinal pathways
“We will study closely related gut bacterial strains that have distinct effects on anti-inflammatory immune responses to understand how gut microbes limit inflammation,” said Dr. Ahern, assistant staff in the Department of Cardiovascular & Metabolic Sciences.
Through the use of state-of-the-art core facilities within the Center for Microbiome and Human Health, the researchers will determine if different strains of the gut bacteria Bacteroides thetaiotaomicron—which has been revealed in previous studies to induce the accumulation of anti-inflammatory immune cells—can differentially promote anti-inflammatory responses in the gastrointestinal tract. They will also leverage the genetic manipulability of B. thetaiotaomicron in preclinical IBD models to gain a better understanding of the specific pathways that allow it to promote anti-inflammatory immune function.
“By uncovering the cellular and molecular mechanisms through which intestinal immune cells communicate with the microbiome, we ultimately hope to develop next generation probiotics that combine the beneficial features from different microbes to rebalance the scales of pro- and anti-inflammatory pathways, thereby maintaining homeostasis and preventing the chronic inflammation that leads to IBD,” said Dr. Ahern.
