Henry Krause and Jaibao Liu

9 April 2026

By Kira Belaoussoff

This article was originally published on the Donnelly Centre for Cellular and Biomolecular Research News website.

The Krause Lab at the Donnelly Centre has discovered a new potential treatment avenue for debilitating conditions like Inflammatory Bowel Disease (IBD). By investigating one of the main controllers of lipid storage in the human body, the researchers identified a small molecule produced by gut microbes that protects against colon inflammation. 

It’s the continuation of the Krause Lab’s decades-long search for molecules that bind to a specific family of proteins (nuclear receptors) that regulate a variety of metabolic and inflammatory diseases. This recent research was spearheaded by Donnelly research associate Jiabao Liu, who developed a new method to identify these interacting molecules over a decade ago and has been following up the hundreds of different molecules identified ever since. 

“We are trying to resolve a very basic, very general question,” says Liu, the first author of the Nature Microbiology paper. “Can what you eat make you healthier?”

The most recent publication involves a microbial metabolite that binds and activates the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα), which serves as a main regulator of lipid metabolism and storage. 

“Typically, that means taking fatty acids and turning them into triglycerides and storing them in fat tissue,” explains Professor and Donnelly PI Henry Krause. “We’ve been trying to find legitimate, natural ligands that can bind to PPARα and control it. Jiabao has found a few.”

PPARα has other roles as well; as the receptor is abundant in the liver, it is thought to play a major role in fatty liver disease. That has been a major challenge, as past attempts to find ligands that bind to PPARα have resulted in complications like enlarged livers. 

Krause explains, “We think it’s because they’ve been using artificial ligand mimics that either activate PPARα too strongly or activate it in ways that it starts to regulate targets that it wouldn’t normally target.” 

As there are no current long-term treatments for IBD because of these issues, the Krause group is eager to find one without negative side effects. 

“IBD is a bowel disease, so we started by searching for active molecules from the stools of IBD patients,” says Liu. “We found one oleic acid metabolite produced by our gut microbes called 10-oxostearic acid, or 10-oxoSA. “

Oleic acid is the most prevalent fatty acid in nature and is abundant in foods like olive oil and certain nuts, fruits, and animal products. 

Liu continues, “10-oxoSA is the most potent PPARα regulator identified so far. This gave us the idea that gut bacteria can convert a not strong ligand—oleic acid—to a very potent ligand—10-oxoSA.” 

To test 10-oxoSA’s potential for IBD prevention, the group treated mice with chemically induced colitis—inflammation of the inner lining of the colon—and found that 10-oxoSA had beneficial effects with none of the detrimental side effects caused by previously used PPARα activators. 

“Because humans produce oxoSA as a natural microbial byproduct all the time, we considered it made sense that it was safer compared to the synthetic drugs,” says Liu. “The results tell us it is.” 

Liu is pleased with the results, but he’s already moving on to different research paths to further investigate the ways our diet can improve our health. 

“Jiabao reads voraciously, so he’s always finding new stuff,” says Krause, smiling. “His approach worked beautifully and he’s still got a whole line of new compounds to test. He finishes one story, he’s onto the next, and he tries to decide which path is the next most interesting one.” 

“New targets, new natural ligands,” Liu says. “If we can figure out what’s in our diet, and how it may produce safer, cheaper strategies to prevent disease, we can postpone our disease.” 

Read the full paper, published in Nature Microbiology.