Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616, USA.
Science. 2018 Nov 30;362(6418). doi: 10.1126/science.aat9076.
An imbalance in the colonic microbiota might underlie many human diseases, but the mechanisms that maintain homeostasis remain elusive. Recent insights suggest that colonocyte metabolism functions as a control switch, mediating a shift between homeostatic and dysbiotic communities. During homeostasis, colonocyte metabolism is directed toward oxidative phosphorylation, resulting in high epithelial oxygen consumption. The consequent epithelial hypoxia helps to maintain a microbial community dominated by obligate anaerobic bacteria, which provide benefit by converting fiber into fermentation products absorbed by the host. Conditions that alter the metabolism of the colonic epithelium increase epithelial oxygenation, thereby driving an expansion of facultative anaerobic bacteria, a hallmark of dysbiosis in the colon. Enteric pathogens subvert colonocyte metabolism to escape niche protection conferred by the gut microbiota. The reverse strategy, a metabolic reprogramming to restore colonocyte hypoxia, represents a promising new therapeutic approach for rebalancing the colonic microbiota in a broad spectrum of human diseases.
肠道微生物群落失衡可能是许多人类疾病的根源，但维持体内平衡的机制仍难以捉摸。最近的研究结果表明，结肠细胞代谢起着控制开关的作用，介导着体内平衡和生态失调群落之间的转变。在体内平衡期间，结肠细胞代谢被导向氧化磷酸化，导致上皮细胞高耗氧量。由此产生的上皮缺氧有助于维持以需氧菌为主的微生物群落，这些细菌通过将纤维转化为宿主吸收的发酵产物提供益处。改变结肠上皮代谢的条件会增加上皮细胞的氧合作用，从而促使兼性厌氧菌的扩张，这是结肠生态失调的标志。肠道病原体颠覆结肠细胞代谢，以逃避肠道微生物群赋予的生态位保护。相反的策略，即代谢重编程以恢复结肠细胞缺氧，代表了一种有前途的新治疗方法，可以在广泛的人类疾病中重新平衡结肠微生物群落。
