This Natural Gut Compound Could Point to More Targeted Treatments for IBD

Researchers at the University of Louisville have identified how urolithin A (UroA), a compound produced when certain gut microbes break down foods such as pomegranates, walnuts and berries, helps protect the intestinal lining — a discovery that could point toward more precise treatments for inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. IBD damages the gut's protective barrier, letting bacteria and other irritants move into places they should not, fueling chronic inflammation and long-term complications; many current treatments work by broadly calming the immune system, which can also weaken normal defenses.

The study, published in Nature Communications, focused on the aryl hydrocarbon receptor (AHR), a protein that responds to signals from food, microbes and the environment. Certain pollutants can activate AHR in harmful ways, but the researchers found that UroA activated it specifically in intestinal epithelial cells — the cells that form the gut's protective surface — switching on the NLRP6 inflammasome, a cellular system often associated with inflammation. In this context, though, the inflammasome did not act as a blunt inflammatory trigger; instead, it helped release controlled levels of molecules involved in gut repair, mucus production, antimicrobial defense and barrier strength.

UroA is not found ready-made in pomegranates or walnuts; it is produced only after gut microbes transform plant compounds called ellagitannins and ellagic acid, meaning two people who eat similar foods can produce very different amounts of UroA depending on the microbes living in their intestines. "The findings show that not all inflammatory pathways are harmful," said Sweta Ghosh, previously a postdoctoral researcher in the study's lead lab and lead investigator on the study. "Under the right conditions and in the right cells, these pathways can play an essential role in maintaining gut health and supporting tissue repair."

The team tested the mechanism in cell studies, organoids and intestinal tissue samples from patients with IBD, and found UroA activated the same protective pathway in human tissue. "This study helps us better understand how natural compounds produced through interactions between diet, gut microbes, and the body can influence disease processes," said Venkatakrishna Rao Jala, the study's lead author and associate professor in the University of Louisville's Department of Microbiology and Immunology. "By identifying this specific protective pathway, we may be able to develop more targeted therapeutic approaches that restore intestinal balance instead of broadly suppressing immune responses."