Healthy intestinal microbiome keeps disease at bay.

healthygutMore and more is focusing on bacteria lining the intestinal lining and their role in preventing disease and invoking a immune response.

A study from the at Yeshiva University has determined that the absorption of a specific bacterial byproduct is crucial for maintaining the 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 , but precisely how they did so wasn’t known.”

Researchers have previously suspected that bacterial metabolites exert their influence by activating a 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 by activating PXR.

The activation of PXR suppressed production of an inflammatory called tumor necrosis factor alpha (TNF-α) while increasing levels of a that strengthens the junctions between adjacent intestinal .

“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 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 Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4. Immunity, 2014; DOI: 10.1016/j.immuni.2014.06.014

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