Desai Mahesh S, Seekatz Anna M, Koropatkin Nicole M, Kamada Nobuhiko, Hickey Christina A, Wolter Mathis, Pudlo Nicholas A, Kitamoto Sho, Terrapon Nicolas, Muller Arnaud, Young Vincent B, Henrissat Bernard, Wilmes Paul, Stappenbeck Thaddeus S, Núñez Gabriel, Martens Eric C
Luxembourg Centre for Systems Biomedicine, Esch-sur-Alzette 4362, Luxembourg; University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg.
University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cell. 2016 Nov 17;167(5):1339-1353.e21. doi: 10.1016/j.cell.2016.10.043.
Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
尽管摄入膳食纤维对健康有益已被认可，但对于纤维缺乏影响肠道微生物群并改变疾病风险的机制，我们知之甚少。我们使用了一种无菌小鼠模型，其中动物被植入了由全序列共生细菌组成的合成人类肠道微生物群，阐明了膳食纤维、肠道微生物群和结肠黏液屏障之间的功能相互作用，结肠黏液屏障是抵御肠道病原体的主要防线。我们发现，在慢性或间歇性膳食纤维缺乏期间，肠道微生物群会将宿主分泌的黏液糖蛋白作为营养来源，导致结肠黏液屏障受到侵蚀。膳食纤维缺乏，再加上因缺乏纤维而侵蚀黏液的微生物群，会促进黏膜病原体鼠柠檬酸杆菌对上皮细胞的更多接触并引发致命性结肠炎。我们的研究揭示了饮食、肠道微生物组和肠道屏障功能障碍之间的复杂途径，利用饮食疗法有望改善健康。
