University HealthCare Alliance

April 12, 2020

Stanford Scientists Link Ulcerative Colitis to Missing Gut Microbes

Bacteria normally inhabiting healthy people’s intestines — and the anti-inflammatory metabolites these bacteria produce — are depleted in ulcerative colitis patients, a Stanford study shows.

About 1 million people in the United States have ulcerative colitis, a serious disease of the colon that has no cure and whose cause is obscure. Now, a study by Stanford University School of Medicine investigators has tied the condition to a missing microbe.

The microbe makes metabolites that help keep the gut healthy.

“This study helps us to better understand the disease,” said Aida Habtezion, MD, associate professor of gastroenterology and hepatology. “We hope it also leads to our being able to treat it with a naturally produced metabolite that’s already present in high amounts in a healthy gut.”

When the researchers compared two groups of patients — one group with ulcerative colitis, the other group with a rare noninflammatory condition — who had undergone an identical corrective surgical procedure, they discovered that a particular family of bacteria was depleted in patients with ulcerative colitis. These patients also were deficient in a set of anti-inflammatory substances that the bacteria make, the scientists report.

A paper describing the research findings was published online Feb. 25 in Cell Host & Microbe. Habtezion is the senior author. Lead authorship is shared by Sidhartha Sinha, MD, assistant professor of gastroenterology and hepatology, and postdoctoral scholar Yeneneh Haileselassie, PhD.

The discoveries raise the prospect that supplementing ulcerative colitis patients with those missing metabolites — or perhaps someday restoring the gut-dwelling bacteria that produce them — could effectively treat intestinal inflammation in these patients and perhaps those with a related condition called Crohn’s disease, Habtezion said.

A clinical trial to determine whether those metabolites, called secondary bile acids, are effective in treating the disease is now underway at Stanford. Sinha is the trial’s principal investigator, and Habtezion is the co-principal investigator.

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