Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, 77030, TX, USA.
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, 77030, TX, USA.
Nat Commun. 2018 Nov 27;9(1):5010. doi: 10.1038/s41467-018-07476-4.
Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2'-fucosyllactose (2'FL), and 6'-siallylactose (6'SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance of Enterobacter/Klebsiella in maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.
新生儿轮状病毒感染主要为无症状感染。虽然在某些情况下与胃肠道症状有关，但影响临床表现差异的因素尚不清楚。本研究采用多学科方法，表明人乳寡糖（HMOs）、乳微生物组和婴儿肠道微生物组之间的复杂相互作用影响新生儿轮状病毒感染。在体外研究中验证了 HMOs 不是新生儿 G10P[11]株的诱饵受体，人群研究显示，胃肠道症状阳性的轮状病毒新生儿母亲的乳汁中 LNT、2'-岩藻糖基乳糖（2'FL）和 6'-唾液酸乳糖（6'SL）水平显著升高。此外，这些 HMOs 与母乳和婴儿粪便中肠杆菌科/克雷伯菌的丰度相关。特定的 HMOs 还可提高新生儿株来源的轮状病毒疫苗的感染力。本研究为宿主因素影响新生儿轮状病毒感染提供了分子和转化方面的见解，并确定了可能促进活减毒轮状病毒疫苗性能的母体成分。
