Poster #11: Connor Tiffany PhD

Healthcare Access and Quality is a Robust Predictor of Infant Gut Microbiota Variation and Pathogen Colonization

Connor R. Tiffany1,2, Alex V. Carr3, Sean Gibbons3, Joseph P. Zackular1,2,4 Affiliations: 1. Children’s Hospital of Philadelphia, Department of Pathology and Laboratory Medicine. 2. Children’s Hospital of Philadelphia, Center for Microbial Medicine. 3. Institute for Systems Biology. 4. Perelman School of Medicine at the University of Pennsylvania, Department of Microbiology.

Early life is a critical window of development and host-microbiome interactions are critical for establishment of a life-long symbiosis. Perturbation to the developing microbiome early in life is associated with increased risk for numerous inflammatory and autoimmune diseases. Moreover, low birthweight infants are at increased risk for colonization and infection with antimicrobial resistant pathogens. Despite the importance of the gut microbiome early in life, the rules shaping healthy succession of a healthy community are still poorly understood. To address this gap in knowledge, we created a database of human infant gut metagenomes of healthy infants from twenty different countries and developed a statistical framework to determine what variables contribute to differences in community structure and functional capacity of the infant gut microbiome. We used age, diet, and environment as predictor variables. For environment, healthcare access and quality (HAQ) scores from the global disease burden study were used as a proxy variable. Our model determined that environment is a better predictor of microbiome differences than age or diet. To explore consequences of differences in community structure and function of the gut microbiome between infants from different environments, we constructed a pathogen colonization index. We found that both high HAQ and low HAQ infants have sub-clinical pathogen colonization, however, there were differences in which pathogens colonized infants from these distinct environments. In silico invasion assays suggest both low and high HAQ infants are equally susceptible to pathogen colonization which suggests exposure could be responsible for differential pathogen prevalence. This work provides a global, comprehensive database of infant gut metagenomes that will serve as a vital resource. Our analysis reveals key factors that determine the rules of pathogen colonization and succession of the microbiome during early life, paving the way for future work aimed at preventing pathogen colonization in infancy."