# Effects of host endocannabinoid signaling on Enterobacteriaceae infection

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $531,747

## Abstract

PROJECT SUMMARY
The Escherichia coli species encompass innocuous commensals, resident pathobionts, and invading
pathogens. In the gut, the proliferation of E. coli and other Enterobacteriaceae, and their potential to induce or
contribute to disease, is dependent on the reduction or complete loss of colonization resistance. Host,
microbial, and environmental factors can all contribute to lowering colonization resistance to facilitate
Enterobacteriaceae expansion, which represents a common hallmark of microbiome dysfunction in many
chronic diseases including Crohn’s disease. Supported by our extensive preliminary data, this proposal will
define a novel mechanism by which a host signaling network – the endocannabinoid system – lowers
colonization resistance by releasing otherwise unavailable nutrients that stimulate proliferation of gut E. coli
pathobionts and Enterobacteriaceae pathogens. Using mouse models of enteric infection and of pathobiont-
exacerbated Crohn’s disease, as well as a combination of host and bacterial genetics, targeted metabolomics,
gnotobiology, and pharmacological manipulations, this proposal outlines an innovative approach to: 1) evaluate
the temporal and spatial effects of host endocannabinoid activity on Enterobacteriaceae niche formation in the
gut and consequent effects on disease; and 2) define the nutrients and bacterial metabolic pathways that
support Enterobacteriaceae expansion stimulated by increased host endocannabinoid activity. These studies
are particularly pressing considering the ongoing efforts to develop the endocannabinoid system as a
therapeutic target for managing debilitating symptoms that are commonly reported in chronic inflammatory
diseases.

## Key facts

- **NIH application ID:** 10944286
- **Project number:** 1R01AI184916-01
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Melissa Ellermann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $531,747
- **Award type:** 1
- **Project period:** 2024-06-06 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10944286

## Citation

> US National Institutes of Health, RePORTER application 10944286, Effects of host endocannabinoid signaling on Enterobacteriaceae infection (1R01AI184916-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10944286. Licensed CC0.

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