# Bacterial metabolites controlling Th17 cells

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $460,084

## Abstract

ABSTRACT
Bile acids are cholesterol-derived, natural surfactants, produced in the liver. They are critical to
lipid digestion, antibacterial defense, and cholesterol synthesis, as well as other aspects of
human biology. Importantly, bile acid dysregulation has been linked to intestinal bowel disease.
Intestinal inflammation is modulated through a fine balance between the intestinal microbiota
and the mucosal immune system. Imbalance can activate immune signaling pathways, leading
to uncontrolled, pathological immune responses. Gut-residing bacteria in both the small and
large intestines are exposed to a significant amount of bile acids and are known to convert host-
derived bile acids into more hydrophobic, and thus, more bioavailable derivatives.
We hypothesize that bacteria-produced secondary bile acids directly regulate the differentiation
and/or function of key immune cells under inflammatory conditions, providing a communications
link between commensal bacteria and mucosal immunity. We propose 1) to dissect the
mechanisms of bile acid-mediated immune modulation and identify bile acid immune cell
targets, 2) to identify bacteria and their enzymes that generate immune-modulatory bile acids
and 3) to identify the novel metabolites of bile acids that regulate mucosal inflammation in vivo,
at physiological concentrations. Elucidation of these mechanisms will not only provide novel
therapeutic options for inflammatory diseases, but also open exciting avenues to study unique
regulatory interactions between gut-residing microorganisms, small molecule metabolites and
host immune cells.

## Key facts

- **NIH application ID:** 9998942
- **Project number:** 5R01DK110559-06
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Jun R. Huh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $460,084
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998942

## Citation

> US National Institutes of Health, RePORTER application 9998942, Bacterial metabolites controlling Th17 cells (5R01DK110559-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9998942. Licensed CC0.

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