Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection

Sasirekha Ramani (), Christopher J. Stewart, Daniel R. Laucirica, Nadim J. Ajami, Bianca Robertson, Chloe A. Autran, Dhairyasheel Shinge, Sandya Rani, Sasirekha Anandan, Liya Hu, Josephine C. Ferreon, Kurien A. Kuruvilla, Joseph F. Petrosino, B. V. Venkataram Prasad, Lars Bode, Gagandeep Kang and Mary K. Estes
Additional contact information
Sasirekha Ramani: Baylor College of Medicine
Christopher J. Stewart: Baylor College of Medicine
Daniel R. Laucirica: Baylor College of Medicine
Nadim J. Ajami: Baylor College of Medicine
Bianca Robertson: University of California, San Diego
Chloe A. Autran: University of California, San Diego
Dhairyasheel Shinge: Christian Medical College
Sandya Rani: Christian Medical College
Sasirekha Anandan: Christian Medical College
Liya Hu: Baylor College of Medicine
Josephine C. Ferreon: Baylor College of Medicine
Kurien A. Kuruvilla: Christian Medical College
Joseph F. Petrosino: Baylor College of Medicine
B. V. Venkataram Prasad: Baylor College of Medicine
Lars Bode: University of California, San Diego
Gagandeep Kang: Christian Medical College
Mary K. Estes: Baylor College of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07476-4

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