A novel therapeutic strategy for treating inflammatory bowel diseases (IBD) would work by removing inflammation-inducing succinate molecules secreted by gut bacteria.

The method is based on findings in the biochemistry and pharmacology lab of Ben-Gurion University of the Negev (BGU) Prof. Ehud Ohana showing increased gut levels of succinate in people with IBD.

Succinate is a metabolic molecule involved in various biochemical cell processes. Several recent studies show that succinate drives inflammation, in particular the inflammatory activity of macrophages, white blood cells in the immune system.

Isolating the succinate molecules and chelating them – a chemical bonding process that helps remove them from the body – is proposed in a study conducted by Moran Fremder, an MD/PhD student in Ohana’s lab, in collaboration with Prof. Jae Hee Cheon from Yonsei University in South Korea.

IBD, primarily Crohn’s disease and ulcerative colitis, affect up to 1.5 % of US adults and millions of people globally and can lead to a severely impaired quality of life and to significant morbidity.

“Current treatments for IBD include antibiotics, steroids and biological treatments aimed at inhibiting the activity of the immune system. Such treatments can have long-term side effects, and none address the root causes underlying IBD, which are largely unknown,” explained Ohana. “Our novel findings show that IBD is driven, at least partially, by changes in the activity of gut bacteria and by the accumulation of succinate in the gut, leading to chronic inflammation. Therefore, chelation of succinate can treat IBD and reduce inflammation.”

Ohana added that his lab’s therapeutic peptides “are identical to molecules that naturally exist in our body and are therefore unlikely to provoke a harmful immune reaction.”

The researchers also propose using biochemical methods to measure succinate concentrations in biological specimens for better diagnosis and monitoring of IBD and related symptoms.

By Abigail Klein Leichman/Israel21c