# Enterotoxigenic Bacteroides fragilis in modulation of host immunity

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $196,875

## Abstract

PROJECT SUMMARY
Humans and other mammals are colonized by a plethora of microorganisms at the time of birth. The
constellation of microorganisms that inhabit the gut is key in the development of the host immune system. It is
increasingly clear that early events in development of the colonic microbiota influence host immunity, nutrition,
and susceptibility to disease, yet specific mechanistic insights on these processes remain limited. Inflammatory
bowel disease (IBD) and colonic malignancy are heterogeneous diseases that emerge as a result of a complex
interplay of host genetic and environmental factors, including the composition and function of the gut
microbiota. Bacteroides fragilis represents up to 2.5% of the human gut microbiota and is often found in
neonates within the first month of life. A subset of Bacteroides fragilis strains termed enterotoxigenic B. fragilis
(ETBF) secretes B. fragilis toxin (BFT), a metalloprotease that causes inflammatory damage of the intestinal
epithelium. ETBF has been found as strongly associated to the pathogenesis of colonic disease, yet also
colonizes up to 20% of asymptomatic humans, suggesting that these individuals may carry a potential long-
term health risk as part of their stable gut microbiome. The primary goal of this proposal is to examine the
effects of early life acquisition of ETBF on the immune system, based on the hypothesis that ETBF can
dramatically alter T cell specific responses. These studies will benefit from the use of a novel model of B.
fragilis vertical transmission in which the temporal and genetic determinants of initial niche colonization by B.
fragilis can be evaluated in neonatal mice. Through a comprehensive genetically- and temporally-dissected
analysis of antigen-specific T cell responses to ETBF during neonatal colonization, this study aims at defining
fundamental principles that underlie ETBF-mediated disease through analysis of luminal antigen sampling and
BFT-dependent modulation of immune response. We will also explore the possibility that ETBF allows for other
members of the microbiota to access the lamina propria niche, further disrupting development of the immune
system. Overall, our proposed studies will provide mechanistic insights of early life effects of BFT on the
immune system, emphasizing the impact on tolerance to Bacteroides-specific and other colonic luminal
antigens.

## Key facts

- **NIH application ID:** 10143907
- **Project number:** 1R21AI157196-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Juliane Bubeck Wardenburg
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,875
- **Award type:** 1
- **Project period:** 2021-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143907

## Citation

> US National Institutes of Health, RePORTER application 10143907, Enterotoxigenic Bacteroides fragilis in modulation of host immunity (1R21AI157196-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10143907. Licensed CC0.

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