# Tolerance defenses in host-microbiota interactions

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2022 · $481,000

## Abstract

Project Summary
The overall goal of this proposal is to understand how host metabolic adaptations during infection promote co-
operative defenses between a host and enteric pathogens to drive asymptomatic carriage and the eventual
evolution of commensalism. The proposed studies utilize a natural in vivo host-pathogen involving a enteric
bacterial pathogen that causes infectious colitis. In previous work, the Ayres lab discovered that host
micronutrient metabolic adaptations during infection with enteric pathogens, regulates host carbohydrate
metabolism leading to a phenomenon the Ayres lab calls “metabolic bribery”. This involves the allocation of
carbohydrates to the niche of the pathogen (intestine) to increase availability for the pathogen to metabolize.
The Ayres lab discovered that the metabolism of these specific carbohydrates by the pathogen suppressed
pathogen virulence and disease, indicating this micronutrient regulation of host and pathogen macronutrient
metabolism acts as an anti-virulence mechanism. In the new proposal, the Ayres lab presents exciting data
demonstrating that micronutrient metabolism coordinates interactions between host glucose and lipid
metabolism to suppress virulence and promote cooperation with enteric pathogens. The proposed studies will
investigate the mechanisms by which dietary micronutrients regulate macronutrient metabolism to suppress
pathogen virulence to yield asymptomatic carriers of the pathogen. The proposed studies will focus on
understanding how micronutrient metabolism orchestrates glucose and lipid processes in the body to suppress
pathogen virulence. The proposed studies will then examine the interplay between the adaptive immune
response and micronutrient mediated cooperative defenses, elucidating how these two systems cooperate to
mediate healthy host-pathogen interactions and protect from infectious colitis. Finally, the proposed studies will
utilize this novel host-pathogen/micronutrient system to elucidate the mechanisms that drive the evolution of
pathogen attenuation towards commensalism and persistence within the microbiota. This work will contribute
to a better understanding for gastrointestinal mucosal adaptive immunology, mechanisms of acute and chronic
gastrointestinal inflammation and colitis, the effects of gastrointestinal microbes and microbial metabolism on
gastrointestinal health and disease, including the effects of pathogenic bacterial pathogens.

## Key facts

- **NIH application ID:** 10378099
- **Project number:** 5R01AI114929-07
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Janelle S Ayres
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $481,000
- **Award type:** 5
- **Project period:** 2015-05-10 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378099

## Citation

> US National Institutes of Health, RePORTER application 10378099, Tolerance defenses in host-microbiota interactions (5R01AI114929-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10378099. Licensed CC0.

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