# Defining the role of S1p and myeloid cells during enterotoxigenic B. fragilis infection

> **NIH NIH R21** · UNIVERSITY OF LOUISVILLE · 2021 · $234,125

## Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) has been associated with acute diarrheal,
inflammatory bowel disease, and colorectal cancer (CRC). ETBF oncogenesis requires the
coordinated action of its toxin, BFT, and an inflammatory response to orchestrate the recruitment
of myeloid cells, but how ETBF recruits colonic myeloid cells remains poorly understood. S1p acts
as bioactive sphingolipid messengers, influencing the myeloid cells migration and regulating
colonic inflammation. However, whether ETBF integrates sphingolipid metabolites to determine
the metabolism of colonic myeloid cells needs to be explored. Recent evidence indicates that
remodeling of myeloid cells metabolism is central to the induction of innate immune response.
We found ETBF infection alters the activity of sphingosine kinase, which is linked to metabolic
remodeling, histone acetylation and PGE2 production in myeloid cells. Two integrated specific
aims are proposed to test: Aim 1 will determine how ETBF infection regulates inflammatory
myeloid cells accumulation in the colon. Aim 2 will determine if ETBF alteration of acetyl-CoA
contributes to metabolic remodeling in myeloid cells via PPARγ activation. Deeper understanding
of the proper role of sphingolipids and their enzymes in controlling the intestinal immune
properties and in promoting the pathogenesis and progression of colitis will generate new
perspectives in the development of “sphingolipid-centered” therapeutic strategies that control the
onset and perpetuation of the ETBF-induced gut inflammation.

## Key facts

- **NIH application ID:** 10369893
- **Project number:** 1R21AI159194-01A1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Zhong-Bin Deng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $234,125
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369893

## Citation

> US National Institutes of Health, RePORTER application 10369893, Defining the role of S1p and myeloid cells during enterotoxigenic B. fragilis infection (1R21AI159194-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10369893. Licensed CC0.

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