The new study points to two factors: the location and the strength of AHR activation. Selectively activating AHR in intestinal epithelial cells through UroA produces protective effects rather than inflammatory damage.

How strong is the evidence?

The team tested the mechanism across several experimental systems:

• Cell studies
• Organoid models (miniature lab-grown gut tissues)
• Intestinal tissue samples from patients with IBD

In human tissue samples, UroA activated the same protective pathway observed in the other experiments.

Lead investigator Sweta Ghosh, previously a postdoctoral researcher in the Jala laboratory, framed the discovery as a reframing of inflammation itself. "The findings show that not all inflammatory pathways are harmful," she said. "Under the right conditions and in the right cells, these pathways can play an essential role in maintaining gut health and supporting tissue repair."

Could this lead to new IBD treatments?

The work raises the possibility that future IBD therapies could target specific protective pathways in selected cell types, rather than broadly suppressing the immune system. Senior author Venkatakrishna Rao Jala, an associate professor in the Department of Microbiology and Immunology and UofL's Brown Cancer Center, said the goal is precision over suppression.

"This study helps us better understand how natural compounds produced through interactions between diet, gut microbes and the body can influence disease processes," Jala said. "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."

What is IBD and why does it matter?

IBD includes Crohn's disease and ulcerative colitis, conditions that affect millions of people worldwide. Both involve persistent inflammation and damage to the intestinal lining. In healthy people, the gut barrier allows nutrients through while preventing harmful bacteria from escaping. In IBD, that barrier breaks down, driving inflammation, pain, and long-term complications.

Jala's earlier work identified the beneficial effects of UroA in the gut. The new study builds on those findings by explaining more precisely how the compound interacts with the immune system to support intestinal health.

The researchers describe their findings as the first demonstration that a natural microbial product can work with the body's own response systems to regulate complex molecular and cellular processes during intestinal injury. The work remains preclinical, and clinical trials in patients would need to confirm safety and efficacy before any urolithin A-based therapy could reach the clinic.