05/17/2021
Dr. Ahern will investigate the interplay between the gut microbiome and host immune response to understand how novel probiotic strategies may help modulate inflammation and one day be used to treat 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.
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.
“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.
Assistant Staff
Lab Profile
Dr. Huang developed an innovative patient-derived model of the chronic inflammatory bowel disease that mirrors the disease’s complexity better than others currently available and identified the protein CXCL8 as an actionable drug target.
Dr. Min and colleagues uncovered a key contribution of regulatory T cells during glucocorticoid-mediated treatment of inflammation, elucidating a possible new, related target for treating aggressive inflammatory diseases.
A new class of gut-restricted, oral therapies that target the enzyme glutamate carboxypeptidase II shows promise in treating inflammatory bowel disease (IBD).
The future of health starts with your support. Donations supply researchers with the tools, space and staff they need to think big.
Give to Cleveland Clinic