# Mechanisms of neonatal IgA production by Lactobacillus reuteri

> **NIH NIH F31** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2020 · $39,519

## Abstract

PROJECT SUMMARY
Microbial interactions with the neonatal immune system influence the trajectory of an individual's health over
the course of a lifetime. The long-term objective of this project is to identify maternal factors, such as
microbiota, that educate the neonatal immune system and direct the balance between tolerance and defense.
Recently, Lactobacillus reuteri, a maternally transferred probiotic species of bacteria, has been implicated in
both exacerbating autoimmunity and raising early neonatal defense by inducing immunoglobulin A (IgA)
production. Immunomodulatory characteristics of L. reuteri vary by strain, and it is unknown whether the
phenomena of exacerbated autoimmunity and induction of early endogenous IgA are limited to those strains
that invoke a pro-inflammatory response. This project aims to clarify the mechanism by which different strains
of L. reuteri induce IgA production, focusing on the contributions of surface antigen and metabolites.
Aim 1: Determine the mechanism of early endogenous IgA induction by L. reuteri. L. reuteri, a gram-
positive organism, has the antigenic potential to stimulate TLR2. TLR stimulation activates B cells, leading to
proliferation of antibody secreting cells. Metabolites produced by L. reuteri stimulate AhR, a transcription factor
associated with enhanced B cell proliferation. A combination of TLR2 and AhR stimulation may optimize
conditions for proliferation of antibody-secreting cells and therefore antibody production.
Aim 2: Translate mechanistic findings with models of the human immune system. B cell physiology varies
by organism. Similarly, L. reuteri strains derived from different species of hosts have unique characteristics.
Therefore, human-derived strains of L. reuteri will be applied to models of the human immune system in vitro
and in vivo.
Aim3: Determine genesis of auto-IgA antibodies by L. reuteri. Strain-dependent induction of early
endogenous IgA will be assessed for autoimmune specificity. Linking the use of L. reuteri as a probiotic on the
maternal-neonatal interface to the inception of autoimmunity would warrant investigation of its safety.
The proposed research will demonstrate the mechanism of early auto-IgA induction by L. reuteri as strain
dependent using a translational model. Training will include specialized techniques for the development of a
humanized mouse model and for the generation of mutant L. reuteri. The majority of research and training will
will occur at the laboratory of Dr. Xin Luo at Virginia Tech. Bacterial mutagenesis training will take place at the
laboratory of Dr. Jan-Peter van Pijkeren at University of Wisconsin-Madison.

## Key facts

- **NIH application ID:** 9992431
- **Project number:** 1F31AT010977-01
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Brianna Swartwout
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,519
- **Award type:** 1
- **Project period:** 2020-05-10 → 2022-05-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992431

## Citation

> US National Institutes of Health, RePORTER application 9992431, Mechanisms of neonatal IgA production by Lactobacillus reuteri (1F31AT010977-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9992431. Licensed CC0.

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