# Defining human gut microbiome-mediated protection against Shigella infection

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $240,750

## Abstract

PROJECT SUMMARY
The diarrheal disease shigellosis impacts 80-165 million individuals and causes an estimated 600,000 deaths
worldwide each year, primarily among children, and no effective vaccines are available. The human gut
microbiome is suspected to play a role in protection against Shigella infection, yet this is largely undefined. We
propose to investigate the role of the human gut microbiome in protection against Shigella both in a novel
mouse model and in culture.
Human challenge studies with Shigella have identified individuals resistant to infection, even among people
assumed to be naive to the pathogen. We will use stool samples collected from humans prior to Shigella
challenge to characterize microbiomes that are sensitive and resistant to Shigella challenge. We will perform
metagenomic sequencing to identify features of interest and transplant these communities into germ-free mice.
We will use Shigella susceptible mice deficient in the NAIP-NLRC4 inflammasome to establish a novel
humanized mouse model for shigellosis and identify factors driving microbiome-mediated protection.
Our preliminary data suggests that specific human bacterial strains can decrease S. flexneri colonization, but
are not as effective as complex human microbiomes, which can provide full protection. We will further
characterize bacterial mechanisms inhibiting Shigella growth and virulence in culture using diverse gut
bacterial culture collections and multiple experimental approaches.
New therapeutic strategies are essential for future prevention and treatment of Shigella given the expansion of
antibiotic resistant strains. This proposal will identify key bacterial species important for Shigella resistance that
can pave the way for microbial therapeutics and prophylactic regimens in high-risk individuals, including
children. It will also establish for the first time a Shigella susceptible mouse model with a human microbiome,
enabling new avenues of research into gut microbiome-Shigella interactions.

## Key facts

- **NIH application ID:** 10952173
- **Project number:** 1R21AI185665-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Ashley Robin Wolf
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $240,750
- **Award type:** 1
- **Project period:** 2024-05-23 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952173

## Citation

> US National Institutes of Health, RePORTER application 10952173, Defining human gut microbiome-mediated protection against Shigella infection (1R21AI185665-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10952173. Licensed CC0.

---

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