Abstract Title
Human milk oligosaccharides and norovirus GII gastroenteritis in a Nicaraguan birth cohort
Presenter
Rebecca Rubinstein, University of North Carolina at Chapel Hill
Co-Author(s)
Rebecca J. Rubinstein (a,b), Lars Bode (c), Yaoska Reyes (a), Nadja A. Vielot (d), Fredman González (e), Christian Toval-Ruíz (f), Lester Gutiérrez (g), MSc, Samuel Vilchez (d), Jessie Edwards (a), Sylvia Becker-Dreps (a,d)*, and Filemón Bucardo (d,h)* ; *=co-senior authors
aDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; bUNC School of Medicine MD-PhD Program, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; cDepartment of Pediatrics, Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), and the Human Milk Institute (HMI), University of California San Diego, La Jolla, California; dDepartment of Family Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; eIndependent Researcher; fFacultad de Ingeniería,Universidad Tecnológica La Salle, León, Nicaragua; gCentro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; hDepartment of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
Abstract Category
Epidemology
Abstract
Introduction: Norovirus exploits α-1,2-fucosylated glycans expressed on the intestinal epithelia of individuals with secretor blood group antigen to establish infection. While the α-1,2-fucosylated human milk oligosaccharide (HMO) 2’-fucosyllactose (2’FL) appears to block norovirus binding in vitro, this relationship has not been tested in longitudinal human cohorts.
Methods: In a Nicaraguan birth cohort, nineteen HMOs were measured in human milk at approximately 1.3 months postpartum using high performance liquid chromatography. We followed children weekly for gastroenteritis and used PCR and Sanger sequencing to detect norovirus GII in diarrheic stools. We then assessed norovirus GII gastroenteritis risk by HMO concentrations and child secretor phenotype over 24 months of follow-up, using multiple imputation to account for missing weekly stool and inverse probability (IP) weighting to account for confounding and differential loss-to-follow-up.
Results: Over 24-months of follow-up, the multiply imputed, IP-weighted incidence of norovirus GII gastroenteritis was 56% (95% confidence interval [CI] 47, 65). Incidence was higher in children of non-secretor mothers (68%) than secretor mothers (54%) and among secretor children (58%) than non-secretor children (25%). Greater precision was achieved in subgroup analyses of child secretors where 2’FL was protective against norovirus GII gastroenteritis, but not in a dose-dependent manner. The α-1,2-fucosylated HMO, lacto-N-fucopentaose-I (LNFP-I), was protective in a dose-dependent manner, while the sialylated HMO, fucosyl-disialyllacto-N-hexaose (FDSLNH), and the non-fucosylated HMO, difucosyllacto-N-hexaose (DFLNH) were associated with a dose-dependent increase in norovirus GII gastroenteritis risk.
Conclusion: The HMO, 2’FL, already available in formula, should be further investigated as an intervention to prevent norovirus GII gastroenteritis.
Methods: In a Nicaraguan birth cohort, nineteen HMOs were measured in human milk at approximately 1.3 months postpartum using high performance liquid chromatography. We followed children weekly for gastroenteritis and used PCR and Sanger sequencing to detect norovirus GII in diarrheic stools. We then assessed norovirus GII gastroenteritis risk by HMO concentrations and child secretor phenotype over 24 months of follow-up, using multiple imputation to account for missing weekly stool and inverse probability (IP) weighting to account for confounding and differential loss-to-follow-up.
Results: Over 24-months of follow-up, the multiply imputed, IP-weighted incidence of norovirus GII gastroenteritis was 56% (95% confidence interval [CI] 47, 65). Incidence was higher in children of non-secretor mothers (68%) than secretor mothers (54%) and among secretor children (58%) than non-secretor children (25%). Greater precision was achieved in subgroup analyses of child secretors where 2’FL was protective against norovirus GII gastroenteritis, but not in a dose-dependent manner. The α-1,2-fucosylated HMO, lacto-N-fucopentaose-I (LNFP-I), was protective in a dose-dependent manner, while the sialylated HMO, fucosyl-disialyllacto-N-hexaose (FDSLNH), and the non-fucosylated HMO, difucosyllacto-N-hexaose (DFLNH) were associated with a dose-dependent increase in norovirus GII gastroenteritis risk.
Conclusion: The HMO, 2’FL, already available in formula, should be further investigated as an intervention to prevent norovirus GII gastroenteritis.