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Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion.
- Source :
-
Science (New York, N.Y.) [Science] 2017 Aug 11; Vol. 357 (6351), pp. 570-575. - Publication Year :
- 2017
-
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.<br /> (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Angiopoietin-Like Protein 4 genetics
Anilides pharmacology
Animals
Anti-Bacterial Agents pharmacology
Butyrates metabolism
Caco-2 Cells
Clostridium drug effects
Clostridium metabolism
Colitis metabolism
Colitis microbiology
Colon metabolism
Colon microbiology
Dysbiosis chemically induced
Dysbiosis genetics
Enterobacteriaceae metabolism
Epithelial Cells metabolism
Epithelial Cells microbiology
Female
Gene Expression
Homeostasis
Humans
Male
Mice
Mice, Inbred C57BL
Nitrates metabolism
Nitric Oxide Synthase Type II antagonists & inhibitors
Nitric Oxide Synthase Type II genetics
Oxidation-Reduction
PPAR gamma antagonists & inhibitors
PPAR gamma genetics
Signal Transduction
Streptomycin pharmacology
Dysbiosis metabolism
Dysbiosis microbiology
Enterobacteriaceae pathogenicity
Gastrointestinal Microbiome
Nitric Oxide Synthase Type II metabolism
PPAR gamma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 357
- Issue :
- 6351
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 28798125
- Full Text :
- https://doi.org/10.1126/science.aam9949