# Population genomic analysis of gut microbial colonization in premature infants.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $635,973

## Abstract

Many studies of the human microbiome underemphasize the complexity of strain-level genetic diversity, partly
due to computational challenges. This is an important problem because subtle genomic alterations can sharply
impact microbial behavior, e.g. antibiotic resistance. Strain-level investigations are needed to understand how
genomes change over time, and also to accurately characterize how microbial communities assemble, respond
to perturbations, and vary among individuals. Our work focuses on the infant gut microbiome to address these
fundamental biologic questions and to identify connections between infant health and early patterns of
colonization. The objective of this project is to use strain-resolved metagenomic analyses to monitor microbial
colonization in the infant gut during the first three years of life. We will test the hypothesis that early
configurations of the infant microbiome can negatively impact maturation of the gut microbiome later in
childhood. If this hypothesis is true, then manipulation of the microbiome in at-risk individuals, particularly
premature infants, may provide opportunities to improve health outcomes. Our proposed work will characterize
the population structure of microbial communities that develop during colonization of the infant gut and
examine the roles of strain persistence, strain immigration, in situ genome diversification, and mobile genetic
elements. To understand major temporal changes in strain or species abundance, we will utilize a novel
method to infer microbial growth rates as well as community wide gene expression. We will conduct strain-
level analyses of fecal samples from 100 newborn infants and their mothers during the first three years of life.
We will include 40 preterm infants with no major medical problems, half born via caesarean section; 40 preterm
infants that develop either necrotizing enterocolitis (NEC) or late-onset sepsis (LOS), half born via caesarean
section; and 20 full term infants, half born via caesarean section. Deep sequencing of microbial DNA will
enable genome reconstruction from coexisting bacterial, archaeal (if present), phage, and plasmid populations.
This will allow us to track species membership, community structure, metabolic potential, and population-level
genetic heterogeneity. We will use these data to test the hypothesis that some early-establishing strains
persist beyond the initial colonization period (Aim 1); to test the hypothesis that stable gut microbial
communities possess higher strain-level diversity than unstable gut microbial communities (Aim 2); and to test
the hypothesis that clinical variables in the newborn period impact patterns of strain acquisition in the first three
years of life (Aim 3). Improved understanding of community assembly and diversification in the infant gut could
translate to improved outcomes by uncovering strategies for disease prevention and treatment. This research
will also reveal universal principles of microbial commun...

## Key facts

- **NIH application ID:** 9961460
- **Project number:** 5R01AI092531-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Jillian Banfield
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $635,973
- **Award type:** 5
- **Project period:** 2011-07-15 → 2021-07-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961460

## Citation

> US National Institutes of Health, RePORTER application 9961460, Population genomic analysis of gut microbial colonization in premature infants. (5R01AI092531-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9961460. Licensed CC0.

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