# Immune interactions with commensal microbes in early life

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $706,668

## Abstract

Project Summary/Abstract
Events in early life, particularly those altering the gut microbiota and immune development, can have an
important role in determining future risk of immune related disorders. For example, it has been reported that the
how substances are encountered by the immune system, the timing of feeding practices, hygiene, and the use
of antibiotics, in early life can modify the risk of immune driven disorders later in life. A common theme amongst
many of these studies is that these risk factors likely affect the developing microbiota. However, the biologic
basis for how early life microbial changes can affect the risk of immune disorders later in life is incompletely
understood. Previous data from our laboratories have suggested that during this preweaning period, specific live
gut bacteria are selectively delivered to the immune system and that interaction of these live bacteria with cellular
immune populations locally in the colonic lamina propria or in distant lymphoid tissues establishes a durable (life-
long) and balanced immune system. In preliminary studies, we observed substantial variance in the amount of
bacterial translocation in this preweaning period, which was corroborated with studies of antigen-specific T cell
responses to a translocating bacterial spp. We therefore hypothesize that the magnitude and quality of the
immune response to these translocating bacteria species during the preweaning period is a stochastic event
during normal ontogeny which represents an important variable in determining whether an individual establishes
a balanced immune system and prevents immune mediated pathologies in later life. However, the nature of
these translocating bacteria and methods to quantify the antigen-specific responses to these bacteria remain a
gap in our knowledge. We will address this question by identifying and characterizing how the translocating
bacteria are encountered by the immune system (Aim 1) and generate reagents to track bacterial antigen
presentation via T cell responses in vivo (Aim 2). We will use these reagents to integrate the immune response
over the preweaning period to translocating bacterial spp. during physiologic development and correlate it with
intestinal immune challenges including infection and experimental colitis in later life (Aim 3). If successful, this
project may reveal that preweaning translocation is an important stochastic developmental variable involved in
generating intestinal immune health and homeostasis.

## Key facts

- **NIH application ID:** 10733457
- **Project number:** 5R01AI173220-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** CHYI S HSIEH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $706,668
- **Award type:** 5
- **Project period:** 2022-11-02 → 2027-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10733457

## Citation

> US National Institutes of Health, RePORTER application 10733457, Immune interactions with commensal microbes in early life (5R01AI173220-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10733457. Licensed CC0.

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