State Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China.
Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China.
Nat Commun. 2021 Jan 11;12(1):271. doi: 10.1038/s41467-020-20673-4.
Dietary patterns and psychosocial factors, ubiquitous part of modern lifestyle, critically shape the gut microbiota and human health. However, it remains obscure how dietary and psychosocial inputs coordinately modulate the gut microbiota and host impact. Here, we show that dietary raffinose metabolism to fructose couples stress-induced gut microbial remodeling to intestinal stem cells (ISC) renewal and epithelial homeostasis. Chow diet (CD) and purified diet (PD) confer distinct vulnerability to gut epithelial injury, microbial alternation and ISC dysfunction in chronically restrained mice. CD preferably enriches Lactobacillus reuteri, and its colonization is sufficient to rescue stress-triggered epithelial injury. Mechanistically, dietary raffinose sustains Lactobacillus reuteri growth, which in turn metabolizes raffinose to fructose and thereby constituting a feedforward metabolic loop favoring ISC maintenance during stress. Fructose augments and engages glycolysis to fuel ISC proliferation. Our data reveal a diet-stress interplay that dictates microbial metabolism-shaped ISC turnover and is exploitable for alleviating gut disorders.
饮食模式和心理社会因素是现代生活方式中无处不在的部分，它们对肠道微生物群和人类健康起着至关重要的作用。然而，饮食和心理社会因素如何协调调节肠道微生物群和宿主的影响仍然不清楚。在这里，我们表明，膳食棉子糖代谢为果糖将应激诱导的肠道微生物重塑与肠干细胞（ISC）更新和上皮稳态联系起来。 Chow 饮食（CD）和纯化饮食（PD）使慢性束缚的小鼠易患肠道上皮损伤、微生物改变和 ISC 功能障碍。CD 优先富集罗伊氏乳杆菌，其定植足以挽救应激引起的上皮损伤。从机制上讲，膳食棉子糖维持了罗伊氏乳杆菌的生长，而罗伊氏乳杆菌反过来又将棉子糖代谢为果糖，从而构成一个正反馈代谢循环，有利于应激期间 ISC 的维持。果糖增强并参与糖酵解，为 ISC 增殖提供燃料。我们的数据揭示了一种饮食-应激相互作用，它决定了微生物代谢塑造的 ISC 更替，可用于缓解肠道疾病。
