Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion
- PMID: 28798125
- PMCID: PMC5642957
- DOI: 10.1126/science.aam9949
Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion
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 γ (PPAR-γ). 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-γ signaling. Microbiota-induced PPAR-γ 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-γ 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.
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Comment in
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Gut cell metabolism shapes the microbiome.Science. 2017 Aug 11;357(6351):548-549. doi: 10.1126/science.aao2202. Science. 2017. PMID: 28798116 No abstract available.
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Microbiome: The microbiota maintains oxygen balance in the gut.Nat Rev Microbiol. 2017 Oct;15(10):574-575. doi: 10.1038/nrmicro.2017.112. Epub 2017 Sep 4. Nat Rev Microbiol. 2017. PMID: 28867820 No abstract available.
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