Human milk oligosaccharides, oral rotavirus vaccine seroconversion, and rotavirus gastroenteritis risk in a vaccinated birth cohort

ObjectiveRotavirus is the leading cause of diarrhea-related mortality in children worldwide and oral rotavirus vaccines (ORVs) have a lower effectiveness in low- and middle-income countries as compared to high-income countries. Novel strategies that leverage natures existing system of protection against rotavirus, such as from human milk, could guide future interventions to reduce global rotavirus burden. The goal of this study was to understand whether human milk oligosaccharides (HMOs) influence ORV response and the risk of rotavirus gastroenteritis in early life. MethodsIn a population-based cohort of 297 Nicaraguan infants followed weekly for 3 years, we assessed the relationships between HMO composition, IgA seroconversion after ORV, and subsequent rotavirus gastroenteritis incidence. ResultsAmong all children, 17.5% experienced [≥] 1 symptomatic rotavirus gastroenteritis episode over 36 months of follow-up. Of the 297 children assessed through serology, only 34.7% seroconverted to the vaccine strain G1P[8]. Seroconverters experienced rotavirus gastroenteritis later and less frequently than non-seroconverters. Receiving milk with higher concentrations of 2-fucosyllactose (2FL) was associated with a greater likelihood of seroconversion to ORV. In contrast, receiving milk with several other fucosylated and sialylated HMOs was associated with decreased seroconversion to ORV. Additionally, receiving milk with higher concentrations of DFLNH (Difucosyllacto-N-hexaose) was associated with a decreased risk rotavirus gastroenteritis in the first 3 years of life, while receiving milk with higher concentrations of lacto-N-fucopentaose (LNFP-I) was associated with an increased risk. ConclusionWhile we found associations between levels of certain HMOs and either ORV seroconversion or rotavirus gastroenteritis risk, the relationships between milk composition, vaccine response, and infection risk are complex and highlight the need for careful safety assessment of HMO supplementation in settings with high rotavirus burden. Article SummaryIn a Nicaraguan birth cohort with low rotavirus vaccine immunogenicity, we evaluated the role of human milk oligosaccharides (HMOs) on rotavirus vaccine seroconversion and rotavirus gastroenteritis risk over the first 3 years of life. Whats Known on This SubjectRotavirus is the leading cause of diarrhea-related mortality in under-5 children worldwide, partly due to poor vaccine immunogenicity in low-and-middle-income countries. Maternal and child genetic secretor status is associated with vaccine response, gastroenteritis susceptibility, and HMO composition in human milk. What This Study AddsThis study revealed that the concentrations of several fucosylated and sialylated HMOs had both positive and negative associations with rotavirus vaccine seroconversion and rotavirus gastroenteritis risk in children. Careful consideration must be taken prior to the use of HMOs as supplements.