TY - JOUR
T1 - Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion
AU - Byndloss, Mariana X.
AU - Olsan, Erin E.
AU - Rivera-Chávez, Fabian
AU - Tiffany, Connor R.
AU - Cevallos, Stephanie A.
AU - Lokken, Kristen L.
AU - Torres, Teresa P.
AU - Byndloss, Austin J.
AU - Faber, Franziska
AU - Gao, Yandong
AU - Litvak, Yael
AU - Lopez, Christopher A.
AU - Xu, Gege
AU - Napoli, Eleonora
AU - Giulivi, Cecilia
AU - Tsolis, Renée M.
AU - Revzin, Alexander
AU - Lebrilla, Carlito B.
AU - Bäumler, Andreas J.
N1 - Funding Information:
We acknowledge the Host-Microbe Systems Biology Core (HMSB Core) at the University of California at Davis School of Medicine for expert technical assistance with microbiota sequence analysis. The data reported in the manuscript are tabulated in the main paper and the supplementary materials. M.X.B. and A.J.Bä. filed invention report number 0577501-16-0038 at iEdison.gov for a treatment to prevent postantibiotic expansion of Enterobacteriaceae. This work was supported by Public Health Service grants AI060555 (S.A.C.), TR001861 (E.E.O.), AI112241 (C.A.L.), DK087307 (C.G.), AI109799 (R.M.T.), AI112258 (R.M.T.), AI112949 (A.J.Bä. and R.M.T.), AI096528
Publisher Copyright:
© 2017, American Association for the Advancement of Science. All rights reserved.
PY - 2017/8/11
Y1 - 2017/8/11
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aam9949
DO - 10.1126/science.aam9949
M3 - Article
C2 - 28798125
AN - SCOPUS:85027175538
SN - 0036-8075
VL - 357
SP - 570
EP - 575
JO - Science
JF - Science
IS - 6351
ER -