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Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. Kelly Caleb J,Zheng Leon,Campbell Eric L,Saeedi Bejan,Scholz Carsten C,Bayless Amanda J,Wilson Kelly E,Glover Louise E,Kominsky Douglas J,Magnuson Aaron,Weir Tiffany L,Ehrentraut Stefan F,Pickel Christina,Kuhn Kristine A,Lanis Jordi M,Nguyen Vu,Taylor Cormac T,Colgan Sean P Cell host & microbe 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. 10.1016/j.chom.2015.03.005
Review article: the role of butyrate on colonic function. Hamer H M,Jonkers D,Venema K,Vanhoutvin S,Troost F J,Brummer R-J Alimentary pharmacology & therapeutics BACKGROUND:Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis. AIM:To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function. METHODS:A PubMed search was performed to select relevant publications using the search terms: 'butyrate, short-chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety'. RESULTS:Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited. CONCLUSION:Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate-mediated effects on colonic function in health and disease. 10.1111/j.1365-2036.2007.03562.x