Characterizing the neonatal nasal microbiome following a parent-to-child nasal microbiota transplant

The Johns Hopkins University received a $401,191 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective June 11, 2025 through May 31, 2027. This research initiative will characterize the neonatal nasal microbiome following parent-to-child nasal microbiota transplant (NMT) procedures conducted under FDA Investigational New Drug (IND) protocols. Using biosamples collected from participating parents and neonates in pilot clinical trials, the research team will determine whether bacterial species from parent anterior nares successfully transfer to, engraft in, and increase diversity within the neonatal nasal microbiome.

The research addresses the urgent clinical challenge of Staphylococcus aureus (S. aureus) colonization and subsequent invasive infections in neonates, which carry a 10–25% mortality rate in very low birth weight infants. Prior preliminary findings indicate that neonates with lower nasal microbiome diversity exhibit increased susceptibility to S. aureus bloodstream infections. The proposed research will provide critical evidence regarding the efficacy and mechanism of action of the first-ever parent-to-child NMT intervention, with potential to inform paradigm-shifting preventive strategies against life-threatening bacterial infections in vulnerable neonatal populations.

Abstract

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.