Sunday, May 11, 2025
5/11/2025
Human milk metabolomics and microbe-host interactions associated with pediatric obesity - PROJECT SUMMARY/ABSTRACT Pediatric obesity affects 1 in 3 children in the US and represents a public health crisis. Accumulating data suggests maternal obesity may seed an “obesogenic” microbiome responsible for transmitting obesity risk from mother to child. Exclusive breastfeeding is associated with protection against pediatric obesity; however, the association between human milk components and the microbiome that account for these observations are poorly characterized. Recent advances in metabolomics analysis provide a novel opportunity to investigate how the human milk metabolome in combination with microbe-host interactions are associated with infant adiposity during the first year of life. The Principal Investigator, Dr. Dominick J. Lemas, Ph.D. will use high-resolution mass spectrometry as a tool to interrogate the human milk metabolome and infant microbiome in a longitudinal maternal-infant cohort of obese and normal weight mothers that includes vaginally and cesarean section deliveries. The over-arching hypothesis of this proposal is that the human milk metabolome will be associated with changes in the early infant microbiome that alter risk for obesity and weight gain in the first year of life. In collaboration with a multidisciplinary team of expert mentors (including primary mentor Dr. Christian Jobin and co-mentors Drs. Josef Neu, Timothy Garrett, William Hogan, Janice Krieger), the primary goal of this K01 career development proposal is for Dr. Lemas to develop expertise in high-resolution metabolomics, biomedical informatics and longitudinal clinical microbiome studies. Specific Aim 1 will determine effective strategies for recruiting pregnant and breastfeeding mothers into clinical microbiome studyes. Specific Aim 2 will characterize the role of the human milk metabolome on the development of the infant microbiome. Specific Aim 3 will identify how the human milk metabolome is associated with infant adiposity. The proposed research is focused on the pathophysiology of infant growth and adiposity during early life and will inform subsequent studies that seek to reduce the risk of pediatric obesity. As outlined in the Justification to Support Extension Request, the COVID-19 pandemic significantly impeded the progress of Dr. Lemas’s K01 award through a combination of delays, shut-downs and general loss of resources, personnel, and opportunities. Ultimately, the COVID-19 pandemic resulted in a cumulative delay of 12-15 months in research and training progress. We are requesting a 12-month extension that will allow Dr. Lemas to complete all project milestones including the training plan that is designed to build an independently-funded clinical and translational research program focused characterizing the microbe-host interactions that contribute to pediatric obesity, consistent with the mission of the NIDDK.
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