Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function
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SUMMARY 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 effects 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.
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- Authors
- Kelly, C. J., Zheng, L., Campbell, E. L., Saeedi, B., 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.
- Affiliations
- University of Colorado Anschutz (US)
- University College Dublin (IE)
- Colorado State University (US)
- University of Bonn (DE)
- Corresponding author
- Colgan, Sean P.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 17
- Issue
- 5
- Pages
- 662-671
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC4433427
- OpenAlex
- W2079183971
- Semantic Scholar
- e050e695ee9a70874a8bce4814a04e75b4ade4ad
- Cited by
- 1,716
- References
- 47
- Citations by year
- 2026: 211 · 2025: 182 · 2024: 202 · 2023: 186 · 2022: 201 · 2021: 199 · 2020: 158 · 2019: 125 · 2018: 106 · 2017: 70 · 2016: 61 · 2015: 11
- FWCI
- 35.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01BX002182)
- Crohn's and Colitis Foundation (327021)
- National Institutes of Health (TL1TR001081, UL1TR001082)
- National Institute of General Medical Sciences (T32GM008497, T32GM007205)
- National Institute of Allergy and Infectious Diseases (T32AI052066)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK096709, R01DK050189, DK104713, DK95491, R01DK099452, R37DK050189, R29DK050189, R01DK103639, R01DK103712, DK-50189, R01DK104713, R01DK095491)
- National Center for Research Resources (TL1RR025778)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- short-chain fatty acids, butyrate, gut microbiota, hypoxia-inducible factor, intestinal epithelium, intestinal barrier function, colonic mucosa, host-microbe interactions, germ-free mice, antibiotic depletion, butyrate supplementation, oxygenation
- MeSH terms
- Animals, Bacteria, Cell Line, Epithelial Cells, Fatty Acids, Volatile, Gene Expression Regulation, Humans, Oxygen Consumption, Mice, Hypoxia-Inducible Factor 1
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