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 R Giulivi, Renee M Tsolis, Alexander Revzin, Carlito B Lebrilla, Andreas J Baumler

Research output: Contribution to journalArticle

162 Citations (Scopus)

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

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Peroxisome Proliferator-Activated Receptors
Peroxisomes
Microbiota
Enterobacteriaceae
Butyrates
Biological Availability
Escherichia
Nitric Oxide Synthase Type II
Salmonella
Nitrates
Energy Metabolism
Colon
Homeostasis
Epithelial Cells
Electrons
Oxygen
Anti-Bacterial Agents
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Byndloss, M. X., Olsan, E. E., Rivera-Chávez, F., Tiffany, C. R., Cevallos, S. A., Lokken, K. L., ... Baumler, A. J. (2017). Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science, 357(6351), 570-575. https://doi.org/10.1126/science.aam9949

Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. / Byndloss, Mariana X.; Olsan, Erin E.; Rivera-Chávez, Fabian; Tiffany, Connor R.; Cevallos, Stephanie A.; Lokken, Kristen L.; Torres, Teresa P.; Byndloss, Austin J.; Faber, Franziska; Gao, Yandong; Litvak, Yael; Lopez, Christopher A.; Xu, Gege; Napoli, Eleonora; Giulivi, Cecilia R; Tsolis, Renee M; Revzin, Alexander; Lebrilla, Carlito B; Baumler, Andreas J.

In: Science, Vol. 357, No. 6351, 11.08.2017, p. 570-575.

Research output: Contribution to journalArticle

Byndloss, MX, Olsan, EE, Rivera-Chávez, F, Tiffany, CR, Cevallos, SA, Lokken, KL, Torres, TP, Byndloss, AJ, Faber, F, Gao, Y, Litvak, Y, Lopez, CA, Xu, G, Napoli, E, Giulivi, CR, Tsolis, RM, Revzin, A, Lebrilla, CB & Baumler, AJ 2017, 'Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion', Science, vol. 357, no. 6351, pp. 570-575. https://doi.org/10.1126/science.aam9949
Byndloss MX, Olsan EE, Rivera-Chávez F, Tiffany CR, Cevallos SA, Lokken KL et al. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science. 2017 Aug 11;357(6351):570-575. https://doi.org/10.1126/science.aam9949
Byndloss, Mariana X. ; Olsan, Erin E. ; Rivera-Chávez, Fabian ; Tiffany, Connor R. ; Cevallos, Stephanie A. ; Lokken, Kristen L. ; Torres, Teresa P. ; Byndloss, Austin J. ; Faber, Franziska ; Gao, Yandong ; Litvak, Yael ; Lopez, Christopher A. ; Xu, Gege ; Napoli, Eleonora ; Giulivi, Cecilia R ; Tsolis, Renee M ; Revzin, Alexander ; Lebrilla, Carlito B ; Baumler, Andreas J. / Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. In: Science. 2017 ; Vol. 357, No. 6351. pp. 570-575.
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