Journal
SCIENCE
Volume 357, Issue 6351, Pages 570-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aam9949
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Funding
- Public Health Service grants [AI060555, TR001861, AI112241, DK087307, AI109799, AI112258, AI112949, AI096528, AI112445, AI114922]
- American Heart Association [15PRE21420011]
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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 gamma (PPAR-gamma). 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-gamma signaling. Microbiota-induced PPAR-gamma signaling also limits the luminal bioavailability of oxygen by driving the energy metabolism of colonic epithelial cells (colonocytes) toward beta-oxidation. Therefore, microbiota-activated PPAR-gamma 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.
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