Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Host Microbe. 2015 May 13;17(5):662-71. doi: 10.1016/j.chom.2015.03.005. Epub 2015 Apr 9.

Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function.

Author information

1
Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
2
School of Medicine and Medical Science, Conway Institute, University College Dublin, Ireland.
3
Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Anesthesiology, University of Colorado, Aurora, CO 80045, USA.
4
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA.
5
Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA; Department of Anesthesiology, University of Bonn, Bonn 53113, Germany.
6
Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
7
Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA. Electronic address: sean.colgan@ucdenver.edu.

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.

PMID:
25865369
PMCID:
PMC4433427
DOI:
10.1016/j.chom.2015.03.005
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center