# Mechanisms Underlying Regulation of Susceptibility to CNS Autoimmunity by Commensal Lactobacillus Species

> **NIH NIH F31** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2021 · $29,604

## Abstract

Project Summary:
Multiple sclerosis (MS) is a chronic autoimmune central nervous system (CNS) disease and the leading cause
of non-traumatic neurological disability in young adults. The cause of MS is complex and cannot be ascribed to
any single gene with over 70% risk attributed to environmental factors. Recent studies identified an imbalance
in the human gut microbiome within MS patients as one such environmental risk, including depletion of the
Lactobacillus genus. Animal models support a causal role for the gut microbiome in MS, though the mechanism
remains unclear. Utilizing a mouse model of MS, we have identified disease resistant and susceptible
microbiomes, with stark differences in Lactobacillus species abundance and notable differences in their
circulating metabolic by-products known to modulate the immune system. Further, we have identified a single
commensal species, Lactobacillus reuteri (L. reuteri), which is sufficient to accentuate MS-like symptoms in the
mouse with whole genome sequencing indicating the necessary enzymatic machinery to account for the
observed differences in circulating metabolites. The focus of this proposal is to 1) determine the cellular
mechanisms underlying the effects of L. reuteri on EAE including both impact on infiltrating peripheral immune
cells and CNS resident glial cells and 2) determine the impact of L. reuteri-derived tryptophan metabolites on
neuroinflammation.
In direct support of the proposed studies, the training plan will develop the knowledge, expertise, scientific
communication skills and technical abilities in 1) mouse models of multiple sclerosis focused on host interactions
with the gut microbiome including directed microbiome manipulation, 2) immunology, with a focus on
neuroimmunology, flow cytometry, and functional assays in vitro and in vivo, 3) microbiology, with a focus on
commensal gut bacteria, their culture, isolation, genomic and metabolic characterization, and manipulation, 4)
neuropathology, with a focus on techniques to investigate CNS pathology to characterize inflammatory
demyelinating lesions in CNS autoimmune disease and blood brain barrier integrity analysis and 5)
metabolomics with a focus on bacterial metabolites and their effects on host physiology.
The training environment at the University of Vermont (UVM) is multidisciplinary with a collegial atmosphere that
stresses active mentorship and as such is uniquely appropriate to support this proposal which bridges
autoimmunity, CNS neuropathology and commensal microbiota. This is evidenced by co-mentors with
appointments in the departments of Biomedical and Health Sciences (BHSC), Microbiology and Molecular
Genetics (MMG), and Neurological Sciences which are connected to a hub of core facilities and the Larner
College of Medicine offering ample opportunity to share resources and promote in-person communication.

## Key facts

- **NIH application ID:** 10312423
- **Project number:** 1F31NS120381-01A1
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Theresa Lynn Montgomery
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $29,604
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312423

## Citation

> US National Institutes of Health, RePORTER application 10312423, Mechanisms Underlying Regulation of Susceptibility to CNS Autoimmunity by Commensal Lactobacillus Species (1F31NS120381-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10312423. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*