Characterizing the Neonatal Nasal Microbiome Following a Parent-to-Child Nasal Microbiota Transplant

Staphylococcus aureus (S. aureus) is a common pathogen causing healthcare associated infections (HAI) in neonates. An estimated 2-3% of very low birth weight infants develop S. aureus bloodstream or central nervous system infections with an overall mortality of 10-25%. During delivery or after birth, S. aureus can transfer from people or the environment and asymptomatically colonize neonates, primarily in the anterior nares. S. aureus colonization is a well-established predisposing factor to invasive, life-threatening infection, with up to one third of S. aureus colonized neonates in the neonatal intensive care unit (NICU) developing a S. aureus infection. Recently, we characterized the nasal microbiome of neonates in the NICU and found that neonates with S. aureus bloodstream infections had an increased relative abundance of S. aureus sequences in nasal swab samples and lower alpha and beta diversity measures compared to neonates with and without S. aureus colonization. These data suggest that a more diverse bacterial community may promote colonization resistance to S. aureus and protect against infection. Our long-term goal is to develop paradigm-changing interventions to prevent life-threatening S. aureus infections in neonates. Recently under an FDA IND, we launched two pilot placebo-controlled trials to test the safety and feasibility of the first-ever parent-to-child nasal microbiota transplant (NMT). Using stored samples collected during these pilot trials, we propose to determine whether bacteria from the parent anterior nares can be transferred to and seed the neonate's nares, engraft in the neonatal microbiome, and increase neonatal nasal microbiome diversity. Our specific aim is to characterize the neonatal nasal microbiome following a parent-to-child NMT. Using samples collected from parents, neonates (prior to and periodically after NMT), and environmental controls, we will perform shotgun metagenomic sequencing to characterize and compare the nasal microbiome of neonates who received NMT or placebo. This study will characterize a novel strategy to assess the biologic plausibility of an NMT. Findings from this work will inform future studies in children and adults to manipulate the nasal microbiome as a strategy to prevent S. aureus colonization and disease. Project Number: 1R21AI179644-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: AARON MILSTONE | Institution: JOHNS HOPKINS UNIVERSITY, BALTIMORE, MD | Award Amount: $401,191 | Activity Code: R21 | Study Section: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21AI17964401A1