# Microbiota metabolites, GPR, and inflammatory bowel diseases

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $348,750

## Abstract

How gut microbiota regulates intestinal homeostasis and the pathogenesis of inflammatory bowel
diseases remains unclear. Emerging evidence suggests that the host immune system can sense bacterial
metabolites in addition to pathogen-associated molecular patterns and that recognition of these small
molecules can influence the host immune response in the context of disease and inflammation in the gut
and beyond. Of particular interest are short-chain fatty acids (SCFAs) such as acetate, n-propionate, and
n-butyrate, which are solely metabolized by gut bacteria from otherwise indigestible carbohydrates, i.e.,
from fiber-rich diets. Moreover, SCFAs have been shown to ameliorate disease in models of
inflammatory bowel disease (IBD) and allergic asthma. Further, SCFAs are associated with reduced risk
of various diseases, including IBD, and dysbiosis in IBD patients was associated with altered SCFA
fermentative pathways. However, the mechanisms involved are still largely unknown. Most notable
among the SCFA targets is the mammalian G protein-coupled receptor pair of GPR41 and GPR43. Our
hypothesis is that SCFAs promote Th1 and Th17 cell production of IL-10 through mTOR and Blimp-1 in
a GPR43-dependent manner, which leads to preservation of intestinal immune homeostasis to microbiota
and inhibition of IBD. Further, the diets supplemented with SCFAs will prevent as well as treat colitis,
through regulation of gut microbiota compositions. We will investigate whether the mechanisms by which
SCFAs promote T effector cell production of IL-10, and loss of GPR43 in microbiota antigen-specific T
effector cells promoting the pathogenesis of colitis. Finally, we will define whether the diets supplemented
with SCFAs prevent as well as treat colitis through regulation of gut microbiota compositions.

## Key facts

- **NIH application ID:** 9961568
- **Project number:** 5R01DK112436-04
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Yingzi Cong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,750
- **Award type:** 5
- **Project period:** 2017-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961568

## Citation

> US National Institutes of Health, RePORTER application 9961568, Microbiota metabolites, GPR, and inflammatory bowel diseases (5R01DK112436-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9961568. Licensed CC0.

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