MedicalResearch.com Interview with:
Sasirekha Ramani, PhD
Molecular Virology and Microbiology
Baylor College of Medicine
MedicalResearch.com: What is the background for this study?
Response: This work pertains to Rotavirus, a leading cause of diarrhea and vomiting in children under the age of 5 years. In this paper, we described our work with a rotavirus strain that almost exclusively causes neonatal infections. For many years, we have been trying to understand why this strain primarily infects newborns and why infection in some babies is associated with gastrointestinal symptoms while others are asymptomatic. A few years ago, we showed that this particular virus binds to developmentally-regulated glycans (sugars) in the gut as receptors. As the baby grows, these sugars get modified, and that potentially explains why infection with this virus is primarily restricted to neonates. However, we didn’t really have to answer to why there are differences in association with clinical presentations.
MedicalResearch.com: What are the main findings?
Response: We know that structurally similar sugars called human milk oligosaccharides (HMOs) are present in mothers’ breast milk. We looked at the effect of HMOs on the infectivity of the neonatal virus on MA104 cells that are widely used to study rotaviruses. Much to our surprise, we found enhancement of viral infectivity in presence of HMOs. This was unexpected primarily because we and others have shown that specific sugars in breast milk can reduce the infectivity of other human and animal rotaviruses.
We next wanted to see if these results are biologically relevant, at a population level. For this, we collected samples from a cohort in mothers and infants at the Christian Medical College in India, where we originally described this strain. The HMO profile of breast milk was determined at Dr. Bode’s lab in the University of California at San Diego. Consistent with our laboratory findings, milk from mothers of symptomatic neonates with rotavirus infection had higher levels of specific HMOs. Since HMOs are important for the microbiome, we looked to see if there were differences in the microbiome of mothers’ milk and the infant gut. Similar to our HMO results, we found that milk from mothers of symptomatic neonates had higher levels of specific bacteria and these bacteria were also seen in the babies stool. All of these data suggest that an interplay between sugars in mothers milk, what microbes are present in milk and in the babies’ gut can influence symptomatic infections in neonates.
Rotavirus vaccines are live, attenuated viruses which means they replicate in a babies gut and produce immunity. We wondered whether HMOs can improve the replication of a rotavirus vaccine called Rotavac that is similar to the neonatal strain being studied in this project. Indeed, specific HMOs improved the replication of Rotavac in cell culture. These discoveries improve our understanding our understanding of factors that influence rotavirus infection, particularly the role of bioactive components in breast milk.
MedicalResearch.com: What should readers take away from your report?
Response: While we have previously shown that certain sugars in breast milk can reduce the infectivity of commonly circulating rotaviruses, here is a paradigm-shifting example of how there are specific strains of viruses that have evolved to utilize host components to their benefit. Our discoveries are an excellent example for the need to study and fully understand maternal factors such as the composition and variation in breast milk components in host pathogen interactions. Knowing exactly how pathogens are trying to take advantage of breast milk components will guide us in stay ahead in the host-pathogen arms-race. It will also help us come up with strategies to understand and improve vaccine response.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Breast feeding provides numerous benefits of the newborn infant, ranging from nutrition to development of immunity. Aside from antibodies, the role of breast milk components such as HMOs and milk microbiome in enteric infections and vaccines is currently under explored. It is important to understand how these factors affect babies’ development, gut health, vaccine response and immunity, so that we can develop more effective strategies to protect our babies from infectious diseases. These are a couple of areas of interest that we are pursuing. Specific to rotavirus, we would like to understand how components of breast milk affect rotavirus vaccine response.
Our goal is to use that knowledge to develop targeted interventions to improve immunity. The second area of interest is to understand how milk components impact the overall health of the newborn gut and it’s response to infectious diseases. These are more mechanistic studies and the goal is to be able to inform clinical practice, particularly in the NICUs.
MedicalResearch.com: Is there anything else you would like to add?
Response: A key aspect of our work is that these findings are tightly linked to public health. The multidisciplinary nature of our team of researchers has allowed us to answer questions about how this unique rotavirus strain infects neonates, confirm the findings in the field and open possibilities to improve the effectiveness of rotavirus vaccines where they are needed the most. Collaborative science that plays to the strengths of the collaborators is essential for advancing science.
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, Mary K. Estes. Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-07476-4
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