# Gut microbiome-mediated small-molecule signaling and resistance to invading microorganisms

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $363,856

## Abstract

The bacterium Vibrio cholerae causes cholera, a devastating diarrhea disease that affects millions of people
worldwide each year. Cholera is endemic in many areas that suffer from poor sanitation, and imposes an
immense burden in terms of mortality and illness, often on those countries least able to afford it. Despite
advances in understanding how V. cholerae causes disease, there is still a lack of mechanisms to prevent the
spread of cholera. Our previous studies have found that specific configurations of the gut microbiome, or the
community of resident bacteria in the gastrointestinal tract of all humans, mediate susceptibility to V. cholerae
infection. We hypothesize that individual differences in commensal microbes may be a risk factor for cholera.
This proposal aims to determine the relationship between the structure of the gut microbiome and the ability of
V. cholerae to colonize and cause disease. Studies of pathogen-microbiome interactions are limited by a lack
of suitable animal models, a problem that is particularly acute for cholera research, as the behavior of the
pathogen differs between many animal models and humans, while other models are limited by cost and
availability. We have begun to adapt a popular and readily accessible animal model of V. cholerae
pathogenesis, the suckling mouse model, to allow for the establishment of human microbiomes prior to
infection. Using these and gnotobiotic adult colonization models, we will determine how human gut
microbiomes drive the biochemical milieu of the gut into pathogen-resistant or susceptible states. These
mechanisms may determine the establishment and composition of the adult gut microbial community, and thus
determine personalized infectious disease risk. These studies will improve the accessibility of models for
studying how gut microbiomes influence bacterial infections of the gut, and identify new targets for prophylactic
and therapeutic manipulations of the gut microbiome to combat V. cholerae.

## Key facts

- **NIH application ID:** 9984849
- **Project number:** 5R35GM124724-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Ansel Hsiao
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,856
- **Award type:** 5
- **Project period:** 2017-08-11 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984849

## Citation

> US National Institutes of Health, RePORTER application 9984849, Gut microbiome-mediated small-molecule signaling and resistance to invading microorganisms (5R35GM124724-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984849. Licensed CC0.

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