title: Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function.
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.
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Caleb J
authors: CJ
authors: Kelly
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Leon
authors: L
authors: Zheng
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Eric L
authors: EL
authors: Campbell
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Bejan
authors: B
authors: Saeedi
authors: School of Medicine and Medical Science, Conway Institute, University College Dublin, Ireland.
authors: Carsten C
authors: CC
authors: Scholz
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Amanda J
authors: AJ
authors: Bayless
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Kelly E
authors: KE
authors: Wilson
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Louise E
authors: LE
authors: Glover
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Anesthesiology, University of Colorado, Aurora, CO 80045, USA.
authors: Douglas J
authors: DJ
authors: Kominsky
authors: Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA.
authors: Aaron
authors: A
authors: Magnuson
authors: Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA.
authors: Tiffany L
authors: TL
authors: Weir
authors: 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.
authors: Stefan F
authors: SF
authors: Ehrentraut
authors: School of Medicine and Medical Science, Conway Institute, University College Dublin, Ireland.
authors: Christina
authors: C
authors: Pickel
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Kristine A
authors: KA
authors: Kuhn
authors: Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Jordi M
authors: JM
authors: Lanis
authors: Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
authors: Vu
authors: V
authors: Nguyen
authors: School of Medicine and Medical Science, Conway Institute, University College Dublin, Ireland.
authors: Cormac T
authors: CT
authors: Taylor
authors: 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.
authors: Sean P
authors: SP
authors: Colgan
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis*; D051379:Mice; D010101:Oxygen Consumption
chemical_list: D005232:Fatty Acids, Volatile; D051793:Hypoxia-Inducible Factor 1