A study from the Albert Einstein College of Medicine at Yeshiva University has determined that the absorption of a specific bacterial byproduct is crucial for maintaining the integrity of the intestinal epithelium, which is responsible for keeping intestinal bacteria and their toxins inside the gut and away from the rest of the body.
“Intestinal bacteria secrete a wide variety of chemicals known as metabolites,” said Sridhar Mani, M.D., co-corresponding author of the paper. “These bacteria and their metabolites were known to influence the intestinal epithelium’s integrity, but precisely how they did so wasn’t known.”
Researchers have previously suspected that bacterial metabolites exert their influence by activating a protein in the intestinal epithelial cell nuclei called the pregnane X receptor (PXR).
In studies involving mice models, the researchers found that a metabolite called indole 3-propionic acid (IPA),produced by commensal bacteria strengthens the intestinal epithelium’s barrier function and prevents its inflammation by activating PXR.
The activation of PXR suppressed production of an inflammatory protein called tumor necrosis factor alpha (TNF-α) while increasing levels of a protein that strengthens the junctions between adjacent intestinal epithelial cells.
“By adding probiotics in the form of IPA-producing bacteria to the intestine or by administering IPA directly, we may be able to prevent or treat IBD and other inflammatory disorders that occur when the intestinal epithelium has been compromised,” said Dr. Mani. “Such a strategy could also be tried for other health problems that may occur when the intestinal epithelium breaks down, including certain forms of liver disease, diabetes, asthma, allergies, obesity and heart disease.”
Madhukumar Venkatesh, Subhajit Mukherjee, Hongwei Wang, Hao Li, Katherine Sun, Alexandre P. Benechet, Zhijuan Qiu, Leigh Maher, Matthew R. Redinbo, Robert S. Phillips, James C. Fleet, Sandhya Kortagere, Paromita Mukherjee, Alessio Fasano, Jessica Le Ven, Jeremy K. Nicholson, Marc E. Dumas, Kamal M. Khanna, Sridhar Mani. Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4. Immunity, 2014; DOI: 10.1016/j.immuni.2014.06.014