# Contribution of phytochemicals to gut symbiont colonization and synthesis of immunomodulatory sphingolipids

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $157,172

## Abstract

PROJECT SUMMARY
Symbiotic microbiota make critical contributions to host immune development. During the first few years of
human life, and the first three weeks in mice, the gut microbiota undergoes dramatic transformation, mostly in
response to changes in the host environment. How temporal changes and mutual host-microbiota adaptations
shape mucosal immunity remains elusive; however, the contribution of environmental factors (such as shifts in
diet over the life course) warrants molecular-level investigation of the effects of prebiotics/probiotics.
We have previously shown that the ubiquitous human gut symbiont Bacteroides fragilis can modulate host colonic
natural killer T (NKT) cell development by producing unique sphingolipids (alpha-galactosylceramides, or
BfaGCs). Under our original R01, we characterized human microbiota-associated mice (HMA mice).
Supplementation of phytochemicals to HMA mice suppressed colonic NKT cell levels in their offspring. Of note,
in adult HMA mice, phytochemical supplementation can transiently induce the abundance of B. fragilis, strongly
implying that induction of B. fragilis during pre- and postnatal stages is critical for colonic NKT cell development.
In the current proposal, we will dissect the time course of early development and investigate the impact of
phytochemicals on the complex microbiota and subsequent mucosal immune development in early life. This
study will provide valuable information on the effect of beneficial microbes in pregnancy in response to prebiotic
factors, as well as the impact of supplementation during gestation / lactation on the microbiota and immune
development of offspring.

## Key facts

- **NIH application ID:** 10624740
- **Project number:** 3R01AT010268-04S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Sungwhan F Oh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $157,172
- **Award type:** 3
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10624740

## Citation

> US National Institutes of Health, RePORTER application 10624740, Contribution of phytochemicals to gut symbiont colonization and synthesis of immunomodulatory sphingolipids (3R01AT010268-04S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10624740. Licensed CC0.

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