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
Mucosal Inflammation Program, University of Colorado, Aurora, CO 80045, USA; Department of Medicine, University of Colorado, Aurora, CO 80045, USA.
School of Medicine and Medical Science, Conway Institute, University College Dublin, Ireland.
Cell Host Microbe. 2015 May 13;17(5):662-71. doi: 10.1016/j.chom.2015.03.005. Epub 2015 Apr 9.
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.
微生物群与远端肠道之间的相互作用是人类健康的基本决定因素。这种相互作用集中在结肠黏膜，并通过产生短链脂肪酸丁酸为宿主上皮细胞提供能量。我们试图确定上皮丁酸代谢在建立远端肠道严格的氧合状况中的作用。细菌衍生的丁酸会影响上皮细胞的氧气消耗，并导致缺氧诱导因子（HIF）的稳定，HIF是一种协调屏障保护的转录因子。抗生素介导的微生物群消耗会降低结肠丁酸和HIF的表达，补充丁酸后两者均可恢复。此外，无菌小鼠对氧敏感染料的保留减少，稳定的HIF也减少。此外，在缺乏HIF的细胞中，丁酸的影响消失，从而将丁酸代谢与稳定的HIF和屏障功能联系起来。这项研究突出了一种宿主-微生物相互作用增强远端肠道屏障功能的机制。
