# Antibiotic disruption of the gut microbiome and immune response in neonatal late-onset sepsis

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2022 · $165,684

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this proposal is to describe a five-year training and mentorship plan to prepare Drew Schwartz, MD,
PhD to become an independent physician-scientist investigator studying the effects of antibiotics on the preterm
neonatal microbiome and host response. Dr. Schwartz obtained combined MD and PhD degrees in the Medical
Scientist Training Program at Washington University School of Medicine in St. Louis where he studied how
uropathogenic E. coli invade bladder cells to cause severe urinary tract infections. After clinical training in
Pediatrics and Infectious Diseases at Washington University School of Medicine and St. Louis Children’s
Hospital, he joined the lab of Dr. Gautam Dantas, PhD, a renowned expert on the microbiome and antibiotic
resistance. Using fecal samples from an established repository of over 70,000 stools from hospitalized neonates,
Dr. Schwartz developed a novel gnotobiotic mouse model of infant microbiome development and disruption. He
colonizes germ-free dams with neonatal stool and treats microbiota-humanized pups with clinically relevant
doses of antibiotics. He has identified that specific microbiome-antibiotic combinations result in mouse death
concomitant with microbiome disruption and immune dysregulation. The central hypothesis is that antibiotic
treatment predisposes infants with certain microbiome and resistome compositions to either bacteremic or
culture-negative late-onset sepsis. The specific aims of the proposal are to: 1) Define the effects of early-life
antibiotics on human infant microbiome maturation, gut mucosal immune response, and vulnerability to
bacteremia, and 2) Determine microbial and immune mechanisms of bacteremic and culture-negative late-onset
sepsis in a neonatal microbiome-humanized mouse model. The proposed studies will utilize microbiome
sequencing, flow cytometry, host immune profiling, and computational modeling to identify modifiable risk factors
to refine antibiotic prescribing in the neonatal intensive care unit with the overall goal of reducing incidence and
mortality from late-onset sepsis. The mentor, Dr. Dantas, will primarily oversee the project providing training on
microbiome analysis, resistome sequencing, and bioinformatic modeling. Dr. Schwartz has assembled an
advisory committee with expertise on neonatal infections, antibiotic treatment, gut microbiome development and
disruption, and mucosal and peripheral immune response to commensal and pathogenic bacteria. The training
plan incorporates achievement of technical expertise, grant writing skills, responsible conduct of research, and
mentorship through one-on-one learning, University-sponsored workshops, and presentation and workshops at
international conferences. Washington University School of Medicine is the ideal training environment given its
extensive track record, outstanding resources, commitment to physician scientists, and necessary expertise to
complete the proposed research. This K08 a...

## Key facts

- **NIH application ID:** 10474354
- **Project number:** 5K08AI159384-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** DREW Joel SCHWARTZ
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $165,684
- **Award type:** 5
- **Project period:** 2021-08-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474354

## Citation

> US National Institutes of Health, RePORTER application 10474354, Antibiotic disruption of the gut microbiome and immune response in neonatal late-onset sepsis (5K08AI159384-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10474354. Licensed CC0.

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