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Microbiome and immune-cell network study will add insights into inflammatory bowel disease treatment

by Denise B. Hensley
The incidence of ulcerative colitis is increasing across the world with an estimated incurred lifetime cost here in the US of $377 billion. The reasons for this sharp climb are multiple – from epithelial barrier dysfunction, microbial sensing and microbicidal dysfunction, gut microbiota-host interactions and alterations in adaptive immunity. Christopher Fan, MD, recently received a Clinical Scholars Award for a three-year study to improve strategies for treatment of chronic inflammatory diseases of the gastrointestinal tract, like ulcerative colitis (UC). He is currently enrolling patients in a biorepository where they will give stool, blood and tissue samples to see how intestinal disease activity changes over time. Dr. Fan is a translational physician-scientist and gastroenterologist in immunotherapy toxicities and inflammatory bowel disease and the Fondren Centennial Assistant Professor of Medicine at the Houston Methodist Academic Institute.
Christopher Fan, MD
Initially, his study will focus on tumor necrosis factor-alpha (TNF-ɑ), a central mediator of inflammation in UC. However, the goal is to extend the study to all classes of medications to treat inflammatory disease. “Our patient data and the biorepository will allow us to do a deep dive into the clinical questions we have,” he says. Dr. Fan pointed out that increased incidence of inflammatory bowel disease has coincided with globalization and industrialization. “Countries, like those in East Asia and South Asia, have gone through or are going through industrialization and now have increased instances of inflammatory bowel disease,” he says. “We will look at all factors such as the gut microbiome and immune cell populations that may predict outcomes.” Dr. Fan says it is critically important to determine factors that predict loss of response to anti-TNF-ɑ. Multiple biologics and small molecule inhibitors can be used to target other components of the inflammatory cascade for the treatment of UC, so understanding failure mechanisms could help direct the choice of second line therapies or choose an alternate line of therapy. Dr. Fan’s study will define algorithms that will help determine what therapies will be the best next drug, with the goal of personalizing care.