Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion

Mariana X. Byndloss, Erin E. Olsan, Fabian Rivera-Chávez, Connor R. Tiffany, Stephanie A. Cevallos, Kristen L. Lokken, Teresa P. Torres, Austin J. Byndloss, Franziska Faber, Yandong Gao, Yael Litvak, Christopher A. Lopez, Gege Xu, Eleonora Napoli, Cecilia Giulivi, Renée M. Tsolis, Alexander Revzin, Carlito B. Lebrilla, Andreas J. Bäumler

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

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 g (PPAR-g). 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-g signaling. Microbiota-induced PPAR-g signaling also limits the luminal bioavailability of oxygen by driving the energy metabolism of colonic epithelial cells (colonocytes) toward b-oxidation. Therefore, microbiota-activated PPAR-g 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.

Original languageEnglish (US)
Pages (from-to)570-575
Number of pages6
JournalScience
Volume357
Issue number6351
DOIs
StatePublished - Aug 11 2017

ASJC Scopus subject areas

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    Byndloss, M. X., Olsan, E. E., Rivera-Chávez, 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., & Bäumler, A. J. (2017). Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science, 357(6351), 570-575. https://doi.org/10.1126/science.aam9949