# Characterizing and Exploiting Ruminococcus gnavus mediated induction of antimicrobial peptides

> **NIH NIH F31** · DUKE UNIVERSITY · 2022 · $27,575

## Abstract

The gastrointestinal tract of humans and other mammals contain a multitude of microorganisms representing a
complex, predominantly symbiotic relationship with the host. With nearly 100 trillion intestinal bacteria with which
humans have coevolved over millions of years, it is clear that the intestine has had success in navigating host–
microbe interactions. As the rise of microbial resistance to antibiotics continues, there is a pressing need for new
therapeutic strategies, awakening an interest in targeting antimicrobial peptides (AMPs) as host defense
molecules. Epithelial AMPs represent an ancient arm of the innate immune system and play a critical role in
maintaining host-microbial interactions. In work recently published by our lab we identified that Ruminococcus
gnavus induces expression of a broad suite of intestinal AMPs, including Reg3γ, Reg3β, lysozyme, and α-
defensin 5. Interestingly, probiotic administration of R. gnavus protects mice against infection with Clostridioides
difficile, a clinically relevant gram-positive pathogen. The overarching objective of this proposal is to investigate
these host–microbiota relationships as an opportunity to bolster endogenous defenses. Therefore, the central
hypothesis for this proposal is that R. gnavus-mediated induction of AMP expression will prevent infection with
intestinal antibiotic-resistant bacteria. I am interested in understanding the underlying mechanism(s) that govern
R. gnavus induction of AMP expression, and whether R. gnavus-induced AMP expression protects against a
variety of antimicrobial resistant pathogens. In Aim 1, I will explore the specific role of Myd88 and IL-22 in R.
gnavus-mediated induction of Reg3γ, Reg3β, lysozyme, and α-defensin 5. In Aim 2, I will determine whether R.
gnavus can protect against vancomycin-resistant enterococci (VRE), C. difficile, and Salmonella typhimurium in
a Reg3γ- or Reg3β-dependent manner. This proposal will aim to bridge discordant findings relating to
mechanisms thought to govern commensal-induced AMP expression and highlight the potential use of probiotic
mediated induction of endogenous AMPs as a therapeutic.

## Key facts

- **NIH application ID:** 10485167
- **Project number:** 5F31AI161989-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Zeni Elizia Ramirez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $27,575
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-03-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485167

## Citation

> US National Institutes of Health, RePORTER application 10485167, Characterizing and Exploiting Ruminococcus gnavus mediated induction of antimicrobial peptides (5F31AI161989-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10485167. Licensed CC0.

---

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