Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, Ishikawa 921-8836, Japan.
Department of Biotechnology and Bioengineering, Technical University of Denmark, Søltofts Plads, DK-2800 Kgs. Lyngby, Denmark.
Sci Adv. 2019 Aug 28;5(8):eaaw7696. doi: 10.1126/sciadv.aaw7696. eCollection 2019 Aug.
The human gut microbiota established during infancy has persistent effects on health. In vitro studies have suggested that human milk oligosaccharides (HMOs) in breast milk promote the formation of a bifidobacteria-rich microbiota in infant guts; however, the underlying molecular mechanism remains elusive. Here, we characterized two functionally distinct but overlapping fucosyllactose transporters (FL transporter-1 and -2) from subspecies . Fecal DNA and HMO consumption analyses, combined with deposited metagenome data mining, revealed that FL transporter-2 is primarily associated with the bifidobacteria-rich microbiota formation in breast-fed infant guts. Structural analyses of the solute-binding protein (SBP) of FL transporter-2 complexed with 2'-fucosyllactose and 3-fucosyllactose, together with phylogenetic analysis of SBP homologs of both FL transporters, highlight a unique adaptation strategy of to HMOs, in which the gain-of-function mutations enable FL transporter-2 to efficiently capture major fucosylated HMOs. Our results provide a molecular insight into HMO-mediated symbiosis and coevolution between bifidobacteria and humans.
人类肠道微生物群在婴儿期建立后对健康具有持久影响。体外研究表明，母乳中的人乳寡糖（HMO）促进了婴儿肠道中双歧杆菌丰富的微生物群的形成；然而，其潜在的分子机制仍不清楚。在这里，我们从 亚种中鉴定出两种功能上不同但有重叠的岩藻糖乳糖转运蛋白（FL 转运蛋白-1 和 -2）。粪便 DNA 和 HMO 消耗分析，结合已发表的宏基因组数据挖掘，揭示了 FL 转运蛋白-2 主要与母乳喂养婴儿肠道中双歧杆菌丰富的微生物群形成有关。与 2'-岩藻糖乳糖和 3-岩藻糖乳糖复合的 FL 转运蛋白-2 的溶质结合蛋白（SBP）的结构分析，以及两种 FL 转运蛋白的 SBP 同源物的系统发育分析，突出了 对 HMO 的独特适应策略，其中获得功能的突变使 FL 转运蛋白-2 能够有效地捕获主要的岩藻糖基 HMO。我们的研究结果为 HMO 介导的双歧杆菌与人类共生和共同进化提供了分子见解。
