# Molecular interactions in the gut microbiota during early life colonization and perturbation

> **NIH NIH R35** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $440,000

## Abstract

PROJECT SUMMARY
The gastrointestinal tract is home to trillions of microorganisms that play an essential role in early life
development and the maintenance of health. Shortly after birth, newborns are rapidly colonized by this
complex microbial community that possesses a rich metabolic potential. Perturbation to assembly of the
microbiota can have major downstream consequences to health. However, the fundamental ecological
principles and molecular processes that underlie establishment of a beneficial and stable microbial community
are largely unknown. Defining the multidimensional interactions in this complex ecosystem has proven
incredibly challenging and has not moved far beyond simple associations. This is in part due to the inherent
complexity and interconnectedness of the microbiota and a lack of fundamental mechanistic studies at this
interface. Moreover, there are limited technologies available to spatially map and study metabolic cross talk
between species in the microbiota. Here, we propose a novel strategy to generate a molecular blueprint of the
metabolic interactions in the assembling microbiota using an innovative pipeline that integrates advanced
imaging metabolomics with comprehensive mechanistic studies. Our objective is to generate a high-resolution
spatial map of metabolites during community assembly and perturbation. We will use this molecular map to
systematically determine the mechanisms of metabolic cross talk between members of the microbiota and
define the role of these interactions in assembly of communities. We will study colonization and deconstruct
mechanisms of community assembly using simple synesthetic microbial communities, gnotobiotics, and
continuous flow cultivar systems. Our goal is to provide a detailed understanding of the spatial localization and
molecular mechanisms of metabolic interactions in the microbiota during early life. Furthermore, we will define
the molecular determinants that confer increased fitness for early life colonizing organisms. Together, this
proposal will provide a framework for understanding the fundamental mechanisms of community assembly in
infants and lead to the development of novel strategies for manipulating microbial communities in early life and
during microbiota-associated disease.

## Key facts

- **NIH application ID:** 10246508
- **Project number:** 5R35GM138369-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Joseph Paul Zackular
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $440,000
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246508

## Citation

> US National Institutes of Health, RePORTER application 10246508, Molecular interactions in the gut microbiota during early life colonization and perturbation (5R35GM138369-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246508. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*