PROJECT SUMMARY / ABSTRACT Childhood obesity is a rapidly expanding concern, with disproportionate impacts on Latino and Black children. Across the life course, the gut microbiome has been associated with obesity risk. In children, events like cesarean section and antibiotic exposure, which alter patterns of vertical microbiome transmission, have been associated with increased obesity risk. The maternal gut microbiome is remodeled during pregnancy and altered by pre- pregnancy BMI, impacting the microbes available in the maternal gut microbiome to be vertically transmitted to the infant. Therefore, Dr. Holzhausen proposes to examine the impact of maternal weight status and preterm birth on vertical microbiome transmission patterns and childhood overweight and obesity. Dr. Holzhausen will build upon existing microbiome, metabolome, and phenotype data from two ongoing, longitudinal studies: the Latino Mother’s Milk Study (L-MMS) and the Atlanta African American Mother Child cohort (AA-MC). In the L- MMS, Dr. Holzhausen will explore the relationships between maternal weight status, strain-level vertical transmission of gut microbes, function of the child gut microbiome, and overweight/obesity outcomes in 198 children. Dr. Holzhausen will also perform integrated multi-omics analysis to identify latent subgroups of children at increased risk for childhood obesity. The AA-MC will serve as a replication cohort to contextualize the generalizability of initial findings and will further extend the analysis to assess whether vertical transmission patterns differ by pre- versus non-preterm birth. Through her training, Dr. Holzhausen will advance her knowledge of techniques to analyze vertical microbiome transmission; gain expertise in metagenomic sequencing and functional pathway analysis of the gut microbiome; gain experience in techniques for integrating multi-omics data; and develop an understanding of the socio-cultural aspects of obesity. To gain these skills, she will complete a multi-faceted training plan incorporating didactic instruction, seminars, extensive hands-on training, and guidance from a diverse advisory committee of respected researchers. This training will complement her expertise in 16S rRNA microbiome analysis and bioinformatics, ensuring the successful establishment of her independent research career. Findings from these studies will improve our understanding of the role of vertical microbiome transmission in the assembly of the infant gut microbiome and its relationship with childhood obesity. Because the gut microbiome is a highly plastic metabolic feature, this work has the potential to lead to the identification of therapeutic targets to prevent childhood obesity. With the proposed study, Dr. Holzhausen is well positioned to take advantage of existing resources to develop independent, complementary projects, designed to fill critical gaps in our understanding of the impacts of maternal weight status and vertical microbiome transmis...