Project Details

Early Career

Status: Funded - Open

Antibiotics disrupt the gut microbiome and immune response, and increase vulnerability to bacteremia

Drew Schwartz, MD, PhD


BACKGROUND: Preterm neonates receive numerous antibiotic courses which decrease microbial diversity, distort the immune system, and increase the likelihood of developing late onset sepsis and bacteremia. In a subset of neonates, the same strain of bacteria can be cultured from the stool prior to bacteremia. GAP: Antibiotics variably affect the neonatal microbiome leading to clinical heterogeneity with minimal predictive biomarkers of susceptibility to bacteremia. HYPOTHESIS: Frequent antibiotic courses delay microbiome development leading to a dysregulated immune response and enrichment of stool organisms that later cause bacteremia. METHODS: I will leverage fecal samples from 39 infants with bacteremia and 78 control neonates who did not experience bacteremia from an exceptionally unique cohort of 977 preterm neonates in the NICU, together with robustly curated metadata, to determine risk factors for bacteremia. I will 1) Characterize human preterm neonatal microbiome disruption, 2) Determine cytokine content and immunoglobulin-A (IgA) binding of potential pathogens in neonatal stools stratified by specific antibiotic-microbiome combinations, and 3) Create computational models inclusive of antibiotics, bacterial species, ARGs, microbiome structure, and immune parameters to identify biomarkers of bacteremia. RESULTS: Pending IMPACT: Identifying neonates prior to bacteremia by sequencing the gut microbiome, identifying potential antibiotic resistant pathogens, and informing antibiotic decision-making would greatly impact the frequency and morbidity due to bacteremia.