Monitoring and Manipulating the Intestinal Microbiome – Lessons From Inflammatory Bowel Disease (IBD)

 

Sasirekha Ramani, PhD

Assistant Professor of Molecular Virology and Microbiology,
Baylor College of Medicine, Houston, Texas, USA

Despite the introduction of vaccines, rotavirus remains a leading cause of severe, dehydrating gastroenteritis in children under the age of five. Recent work from our laboratory and others have demonstrated that genetically regulated differences in histo-blood group antigen (HBGA) glycan expression affect susceptibility to infection with different human rotavirus strains, including vaccine viruses. Since structural analogs to cell surface glycans are present in breast milk, we asked: How do HMOs in breast milk affect rotavirus infectivity, particularly in neonates? Using a multidisciplinary translational science approach involving virologists, structural biologists, glycobiologists, physicians, and epidemiologists, we are testing the hypothesis that complex interactions between intestinal glycan expression during neonatal development and both the breast milk microbiome and HMOs affect susceptibility to neonatal rotavirus infections. Our studies are primarily carried out with a bovine-human reassortant rotavirus strain G10P[11] that almost exclusively infects neonates in India.

Recently, we have begun utilizing a new model of the human gastrointestinal epithelium to answer fundamental questions on how bioactive components in breast milk affect rotavirus infectivity. Advances in the field of stem cell biology have facilitated the development of non-transformed, human intestinal epithelial cultures called HIEs that recapitulate many biological and physiological properties of the human small intestine. We are currently using HIEs to understand the molecular basis of rotavirus- HMO interactions. Our present studies serve as a foundation for future work on understanding the effect of breast milk components on clinically relevant rotavirus strains and vaccines, as well as other enteric pathogens for which glycans are critical for infection.

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Speaker Bio - Sasirekha Ramani, PhD

Dr. Sasirekha Ramani received her PhD from Christian Medical College, Vellore, India. She then completed a postdoc at the Baylor College of Medicine, where she is currently an Assistant Professor in the Department of Molecular Virology and Microbiology. Dr. Ramani has 14 years of research experience studying rotaviruses and noroviruses, the two most important causes of viral gastroenteritis.

Dr. Ramani’s research interests center on maternal and child health, with a focus on gastrointestinal infections and vaccines. The overall goals of her research are to understand factors that contribute to disease susceptibility and to identify mechanisms to improve immune responses to infectious agents and vaccines. A substantial part of Dr. Ramani’s work involves neonatal infections caused by a unique rotavirus strain, G10P[11], that almost exclusively infects neonates in India. Neonatal enteric infections are important globally, and accumulating evidence supports the idea that bioactive components of breast milk, including human milk oligosaccharides (HMOs) and the breast milk microbiome, may be critical in determining if an infection occurs and whether the outcome is symptomatic or asymptomatic. Recently, her laboratory has begun utilizing a new model of the human gastrointestinal epithelium called human intestinal enteroids (HIEs) to answer fundamental questions on how bioactive components of breast milk affect rotavirus infection. Dr. Ramani has authored over 50 published articles and book chapters, and has received a number of awards and honors for her work, including the Alkek Center for Metagenomics and Microbiome Research Pilot Award. She is also the co-principal investigator on grants from the National Institute of Allergy and Infectious Diseases (NIAID) and the Bill and Melinda Gates Foundation.