Microbiota-activated PPAR-{gamma} signaling inhibits dysbiotic Enterobacteriaceae expansion

Perturbation of the gut-associated microbial community may underlie many human illnesses, but the mechanisms that maintain homeostasis are poorly understood. We found that the depletion of butyrate-producing microbes by antibiotic treatment reduced epithelial signaling through the intracellular butyrate sensor peroxisome proliferator–activated receptor (PPAR-). Nitrate levels increased in the colonic lumen because epithelial expression of Nos2, the gene encoding inducible nitric oxide synthase, was elevated in the absence of PPAR- signaling. Microbiota-induced PPAR- signaling also limits the luminal bioavailability of oxygen by driving the energy metabolism of colonic epithelial cells (colonocytes) toward β-oxidation. Therefore, microbiota-activated PPAR- signaling is a homeostatic pathway that prevents a dysbiotic expansion of potentially pathogenic Escherichia and Salmonella by reducing the bioavailability of respiratory electron acceptors to Enterobacteriaceae in the lumen of the colon.

Source: ScienceNOW - August 10, 2017 Category: Science Authors: Byndloss, M. X., Olsan, E. E., Rivera-Chavez, F., Tiffany, C. R., Cevallos, S. A., Lokken, K. L., Torres, T. P., Byndloss, A. J., Faber, F., Gao, Y., Litvak, Y., Lopez, C. A., Xu, G., Napoli, E., Giulivi, C., Tsolis, R. M., Revzin, A., Lebrilla, C. B., Ba Tags: Medicine, Diseases, Microbiology r-articles Source Type: news