Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536.
Yale Microbial Sciences Institute, West Haven, CT 06516.
Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):233-238. doi: 10.1073/pnas.1813780115. Epub 2018 Dec 17.
The composition of the gut microbiota is largely determined by environmental factors including the host diet. Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Silencing by fructose and glucose requires the 5' leader region of the mRNA specifying the protein, designated Roc for regulator of colonization. Incorporation of the leader mRNA in front of a heterologous gene was sufficient for fructose and glucose to turn off expression of the corresponding protein. An engineered strain refractory to Roc silencing by these sugars outcompeted wild-type in mice fed a diet rich in glucose and sucrose (a disaccharide composed of glucose and fructose), but not in mice fed a complex polysaccharide-rich diet. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.
肠道微生物组的组成在很大程度上取决于环境因素,包括宿主饮食。饮食成分被认为通过作为微生物的一部分营养物质来影响肠道微生物组的组成,从而促进其扩张。然而,我们现在报告说,饮食中的果糖和葡萄糖,它们在西方饮食中很常见,专门沉默了一种蛋白质,这种蛋白质对于人类肠道共生菌的定植是必需的,但对于利用这些糖是不必要的。果糖和葡萄糖的沉默需要指定为 Roc(定植调节剂)的 mRNA 前体区域,该 mRNA 专门指定该蛋白质。将 5' 前导 mRNA 掺入异源基因足以使果糖和葡萄糖关闭相应蛋白质的表达。一种对这些糖的 Roc 沉默具有抗性的工程菌株在喂食富含葡萄糖和蔗糖(由葡萄糖和果糖组成的二糖)的饮食的小鼠中竞争优于野生型,但在喂食富含复杂多糖的饮食的小鼠中则不然。我们的发现强调了逃避宿主肠道吸收并到达微生物群的膳食糖的作用:有益微生物对肠道定植的调节独立于为微生物群提供营养。