Sugar and microbiome in breast milk influence neonatal rotavirus infection-ScienceDaily

"Rotavirus infection causes diarrhea and vomiting mainly in children under 5 years of age, with the exception of infants less than 28 days of age who generally have no symptoms. newborns are associated with serious gastrointestinal problems What factors The differences between newborns with and without symptoms are not clearly understood, "said Dr. Sasirekha Ramani, corresponding author, assistant professor of molecular virology and Microbiology at Baylor College of Medicine. "We began our investigation several years ago by determining that a particular strain of rotavirus was associated with both asymptomatic infections and clinical symptoms in newborns."

Ramani and his colleagues first looked for answers from the point of view of the virus. They examined whether factors such as the amount of virus in neonates or their genome might be related to the presence of symptoms in neonates, but found no link between these factors. The researchers then asked the question from the point of view of the newborn. Are there any factors in newborns that could explain why this virus infects newborns and why there are differences in clinical presentation?

In the laboratory, researchers investigated whether maternal breast milk components could inhibit infection of MA104 cells, a well-established model for rotavirus studies, with the rotavirus strain they had identified in nursery rotunda. newborns in India. Unexpectedly, they discovered that certain sugars found in breast milk reinforced the infection of cells in culture with the neonatal rotavirus strain.

"We were surprised by these results," Ramani said. "It is known that breast milk strengthens the protection of the newborn against rotavirus infection and that the presence of sugars in breast milk can reduce the infectivity of other rotaviruses, but we found the opposite for this particular strain of the virus. "

The researchers then returned to the field to determine if they could validate laboratory findings in a cohort of mother-child pairs.

"We found that some of the same specific sugars in breast milk that increase the infectivity of cells in culture are present in the milk of mothers of newborns with symptomatic infection," Ramani said.

In addition, the researchers found an association between the microbiome in breast milk and the gastrointestinal symptoms in the newborn, which sparked new questions, Ramani explained. How does the microbiome contribute to differences in gastrointestinal symptoms?

"What's most interesting for us is that these sugars also increase the replication of the live attenuated vaccine against rotavirus, similar to the neonatal virus we are studying," Ramani said. "An improved viral replication can potentially result in a more effective immune response against the virus, which would better protect the infant, and we hope to explore it in the future as this may inform strategies to improve the effectiveness of rotavirus rotavirus vaccines. " parts of the world where they are not doing well. "

"One of the most important points for us is that these unexpected discoveries are closely related to public health," said co-author Mary K. Estes, Cullen Foundation Professor and Chairholder of Human and Molecular Virology from Baylor College of Medicine and Emeritus. founding director of the Texas Medical Center Digestive Diseases Center. "The multidisciplinary nature of our team of researchers has allowed us to answer questions about how this unique rotavirus strain infects newborns, confirm findings in the field, and pave the way for newborn infestations. improving the effectiveness of rotavirus vaccines where they are needed most. "

"These findings are a perfect example of the urgent need to improve our understanding of the composition and variations of breast milk components," said co-author Dr. Lars Bode, associate professor of pediatrics and director and chair. Collaborative Human Milk Research at Larsson-Rosenquist Foundation, Center for Excellence in Breastmilk and Infant Research, University of California at San Diego. "Understanding how rotaviruses and other pathogens can benefit from the components of breast milk will guide the development of new vaccination strategies to stay ahead of the arms race between pathogens and hosts."

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 and Kurien A. Kuruvilla also contributed to this work . , Joseph F. Petrosino, BV Venkataram Prasad and Gagandeep Kang. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine; University of Newcastle; University of California at San Diego; Christian Medical College, India and Institute of Translation in Health Technology and Science, India.

This work was funded by the National Institutes of Health (grants R01AI105101 and AI36040) and a pilot project of the Center for Metagenomics and Microbiome Research. The authors also warmly thanked the Larsson family – Rosenquist Foundation.