# Bacterial Metabolic Exchanges in Gut Enrichment Culture

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $119,340

## Abstract

Project Summary
The microbial community in the human gut plays a key role in complex disease states, with less diverse
microbiomes observed in obesity, inflammatory bowel disease, and even mental health. However, the specific
interspecies interactions that drive gut community structure, leading to beneficial or deleterious microbiomes,
remain poorly understood. There is, therefore, an urgent need to map these microbial interspecies interactions,
in order to identify key nutrients that could be leveraged to shape microbiomes towards beneficial health
outcomes. Nevertheless, direct study of these communities is difficult: in vivo models of the human microbiome
in mice remain close analogues, but their low-throughput, complex, and expensive nature prevents systematic
dissection of individual components of an in vivo microbiome. In contrast, pure culture studies have illuminated
a wide variety of nutritional requirements and pinpointed potential interspecies interactions, such as those
involving the Vitamin B12 family of cofactors known as corrinoids. Nevertheless, many bacteria have not been
successfully isolated because a required nutrient remains unknown, and pure culture studies remove the
native community nutrients that can alter growth and metabolism. Enrichment cultures, which are simplified
microbial communities that grow out of inoculation, represent an attractive stepping stone that combine the
high-throughput capabilities of pure culture methods with medium complexity. Some bacteria readily grow in
these enrichment cultures but are unable to be isolated axenically in the culture medium, suggesting that many
natural interspecies interactions remain.
The overarching goal of this proposal is to elicit a comprehensive understanding of microbial interactions in the
gut by exploiting the potential of in vitro derived gut enrichment communities for use in high-throughput
discovery. In the first approach, I will determine the impact that corrinoid producer growth has on community
assembly and response to nutritional perturbation (Aim 1) . Second, I will perform a high-throughput isolation
campaign to identify growth factors for `unculturable' bacteria that readily grow in the enrichment culture, and
identify the community members that produce these growth factors (Aim 2). Finally, I propose to directly map
physical interactions in enrichment cultures by exploiting the high-specificity recognition capability of nucleic
acids to perform targeted pulldowns of a given species from the enrichment culture (Aim 3). Successful
completion of these approaches will identify nutritional strategies to perturb the microbiome that may be
leveraged for the treatment of microbiome-related disease.

## Key facts

- **NIH application ID:** 10695152
- **Project number:** 5K99GM143653-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Zachary Hallberg
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $119,340
- **Award type:** 5
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10695152

## Citation

> US National Institutes of Health, RePORTER application 10695152, Bacterial Metabolic Exchanges in Gut Enrichment Culture (5K99GM143653-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10695152. Licensed CC0.

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