Scientists at the Ben-Gurion University of the Negev (BGU) in Israel and Yonsei University in Seoul have identified a potential strategy to treat inflammatory bowel diseases (IBD). The method involves using peptides to reduce the effects of succinate, a proinflammatory molecule that gut bacteria release. The breakthrough could lead to a companion tool to diagnose and treat inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease.
The gut levels of succinate are considerably higher in macrophages of IBD patients, according to BGU professor Ehud Ohana. Furthermore, IBD patients have altered succinate-metabolizing bacteria that likely results in inflammation-inducing succinate surges. The international research team reported slowing succinate absorption by deploying peptide sequences that mimic the binding site within succinate binding enzymes.
The researchers developed a method of targeting and chelating surplus succinate in IBD patients. To do so, they used peptide sequences mimicking succinate binding sites.
Pharmaceutical companies also use succinate as an excipient. “Such treatments can have long-term side effects, and none address the root causes underlying IBD, which are largely unknown,” Ohana said in a statement. After ascertaining that IBD is at least partially the result of gut bacteria changes and succinate build-up, chelation could reduce the chronic inflammation at the heart of IBD. “Furthermore, our therapeutic peptides are identical to molecules that naturally exist in our body and are therefore unlikely to provoke a harmful immune reaction,” Ohana added.
The international research team is optimistic that their research will provide an alternative to antibiotics, steroids and biological treatments deployed for IBD.
A Cell Reports study summarizes the findings.