# Exploiting the microbiota-stromal cell axis for microbiota-targeted medicine

> **NIH NIH DP2** · WASHINGTON UNIVERSITY · 2024 · $466,500

## Abstract

PROJECT SUMMARY
 The development of successful vaccines is a significant achievement in public health. However, vaccines
exhibit varying efficacy across different individuals and populations. Vulnerable groups such as infants, the
elderly, immunocompromised individuals, and those in low- and middle-income countries often experience
suboptimal vaccine responses. Research suggests that the gut microbiota, the community of microorganisms in
the digestive tract, plays a crucial role in shaping immune responses to vaccines. The composition of the gut
microbiota varies significantly among individuals, and its diversity and stability tend to decrease in infancy and
with age, correlating with reduced vaccine responsiveness. This has led to a growing interest in exploring cost-
effective microbiota-targeted interventions to enhance vaccine effectiveness, especially in at-risk populations.
However, the precise mechanisms by which the gut microbiota influences host immunity, particularly B cell
responses, remain poorly understood, posing a significant barrier to unlocking the therapeutic potential of the
microbiota. Recent research has highlighted the role of stromal cells as key mediators in initiating, sustaining,
and concluding B-cell responses. My prior study found that distinctions in intestinal microbiota composition have
been observed to affect immune responses by mediating stromal cells' function, underscoring the ability of
stromal cells to detect microbiota differences and orchestrate immune responses accordingly. Building upon
these insights, I hypothesize that stromal cells play a pivotal role in sensing microbiota differences and
establishing the appropriate immune environment for B-cell development. To test this hypothesis and
uncover the molecular mechanisms involved, this proposed project will leverage the microbiota-stromal cell axis
to identify bacterial strains or molecules that enhance stromal cell function to promote B-cell responses and
antibody production following vaccination. This research will employ a well-established gnotobiotic mouse model
in which germ-free mice are colonized with human-derived microbiota that transmit the high or low
responsiveness to oral cholera vaccines (OCV) of their donors. Through a combination of novel animal models,
stromal cell–specific culture systems, microbiota analysis, single-cell RNA sequencing, and proteomics, we will
1) Identify the gut stromal cell populations that fail to produce essential immune factors for B-cell development
and antibody production 2) Identify microbial components that are crucial for stromal cell development and
activation. The successful completion of this research will a) provide a proof-of-concept that the gut microbiota
can influence stromal cell activation, thereby affecting vaccine responses in both the gut and extraintestinal sites,
b) Lay the groundwork for the development of novel immunostimulatory microbial components that can
significantly enhance stromal cell ...

## Key facts

- **NIH application ID:** 10951348
- **Project number:** 1DP2AI184835-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Meng Wu
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $466,500
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951348

## Citation

> US National Institutes of Health, RePORTER application 10951348, Exploiting the microbiota-stromal cell axis for microbiota-targeted medicine (1DP2AI184835-01). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10951348. Licensed CC0.

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