Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function

Caleb J. Kelly, Leon Zheng, Eric L. Campbell, Bejan J. Saeedi, Carsten C. Scholz, Amanda J. Bayless, Kelly E. Wilson, Louise E. Glover, Douglas J. Kominsky, Aaron Magnuson, Tiffany L. Weir, Stefan F. Ehrentraut, Christina Pickel, Kristine A. Kuhn, Jordi M. Lanis, Vu Nguyen, Cormac T Taylor, Sean P. Colgan*

*Corresponding author for this work

Research output: Contribution to journalArticle

396 Citations (Scopus)

Abstract

Interactions between the microbiota and distal gut are fundamental determinants of human health. Such interactions are concentrated at the colonic mucosa and provide energy for the host epithelium through the production of the short-chain fatty acid butyrate. We sought to determine the role of epithelial butyrate metabolism in establishing the austere oxygenation profile of the distal gut. Bacteria-derived butyrate affects epithelial O2 consumption and results in stabilization of hypoxia-inducible factor (HIF), a transcription factor coordinating barrier protection. Antibiotic-mediated depletion of the microbiota reduces colonic butyrate and HIF expression, both of which are restored by butyrate supplementation. Additionally, germ-free mice exhibit diminished retention of O2-sensitive dyes and decreased stabilized HIF. Furthermore, the influences of butyrate are lost in cells lacking HIF, thus linking butyrate metabolism to stabilized HIF and barrier function. This work highlights a mechanism where host-microbe interactions augment barrier function in the distal gut.

Original languageEnglish
Pages (from-to)662-671
JournalCell host & microbe
Volume17
Issue number5
DOIs
Publication statusPublished - 13 May 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

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    Kelly, C. J., Zheng, L., Campbell, E. L., Saeedi, B. J., Scholz, C. C., Bayless, A. J., Wilson, K. E., Glover, L. E., Kominsky, D. J., Magnuson, A., Weir, T. L., Ehrentraut, S. F., Pickel, C., Kuhn, K. A., Lanis, J. M., Nguyen, V., Taylor, C. T., & Colgan, S. P. (2015). Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell host & microbe, 17(5), 662-671. https://doi.org/10.1016/j.chom.2015.03.005