Mice treated with a chemical that inhibits soluble epoxide hydrolase (sEH) are less prone to intestinal injuries caused by a high-sucrose diet, according to NIEHS-funded research.

Specifically, this treatment worked by reducing colon inflammation and strengthening the gut barrier. The study was published Nov. 18 in the journal Proceedings of the National Academy of Sciences.

“For my lab, our excitement is that the paper shows the soluble epoxide hydrolase drugs — developed largely with NIEHS funding — work on yet another inflammatory disease model,” said senior study author Bruce Hammock, Ph.D., distinguished professor of entomology at the University of California, Davis. “The story may be that overconsumption of sucrose can make inflammatory bowel disease worse.”

Tackling temptation

The impact of diet on health has been gaining increasing attention worldwide. High sucrose, together with high fat, is a typical feature of the Western diet. A high-sucrose diet, including food and beverages rich in sucrose, has been commonly found as a risk factor for a variety of illnesses, such as obesity, insulin resistance and glucose intolerance, fatty liver, inflammation, and many other chronic diseases. However, the molecular mechanisms underlying organ injuries that are mediated by a high-sucrose diet remain largely unknown.

To fill this knowledge gap, Hammock and his collaborators measured metabolites in mice that were fed a high-sucrose diet for 16 weeks. This diet injured the gut barrier and caused colon inflammation, as well as an increase in the sEH enzyme in colon tissue. Treatment with a chemical inhibitor of sEH, and a genetic intervention that deactivated the sEH gene in the intestine, lowered colon inflammation and improved the gut barrier, and in so doing, reduced gut injuries triggered by the sugary diet.

“This study extends our understanding of the potential application of sEH inhibitors, perhaps a diet rich in natural sEH inhibitors — for example, capsaicin, macamides, and their source materials — could benefit people with a fondness for a high-sucrose diet,” said Hammock.

From bench to bedside

According to Hammock, the most exciting aspect of this study is that the researchers expect to embark on their first efficacy trial in humans with the sEH inhibitor.

“The NIEHS RIVER [Revolutionizing Innovative, Visionary Environmental health Research] award has been a wonderful program,” Hammock added. “It gave the flexibility to use good basic research on environmental chemistry and health to find a possible drug for inflammatory bowel disease.”

NIEHS first funded Hammock’s research in 1975 and the same grant continues to be funded. The institute also provided an early Small Business Innovation Research grant, which Hammock said allowed him to translate his research to the clinic.