# Intermittent Fasting-induced Gut Microbiome Modulation of CNS Autoimmunity

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $346,172

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term objectives of the proposed project are to determine the role of the gut microbiome in multiple
sclerosis (MS), as well as to develop dietary and gut microbiome-based therapeutic strategies for this disease.
MS is a chronic autoimmune disease targeting the central nervous system. It affects 2.5 million people
worldwide with significant personal and socioeconomic burdens. Current treatments are usually inadequate;
thus there is a need for new therapeutic approaches. One potential therapeutic strategy is dietary
manipulation. Preliminary studies show that intermittent fasting confers protection to experimental autoimmune
encephalomyelitis (EAE), a murine model for MS, but the underlying mechanisms of protection are unknown.
Microbial analysis revealed beneficial changes in the gut microbiome including increased bacteria diversity and
increased levels of immuno-modulatory bacteria that could dampen the autoimmune response. In addition,
changes in microbial metabolites could contribute to a reduction in autoimmunity. Our preliminary studies
revealed that mice undergoing intermittent fasting produced less fecal acetate, a short-chain fatty acid that was
reported to increase the production of a pro-inflammatory adipokine (leptin) in a G protein-coupled receptor 41-
dependent manner. Importantly, the protective effects associated with the altered microbiome could be
transferred from fasting mice to non-fasting mice through fecal microbial transplants. In a pilot trial we just
concluded, intermittent fasting in MS patients induced changes in the gut flora and leptin levels recapitulating
what we observed in mice with EAE. The proposed studies will delineate the potential pathways by which
changes in the gut microbiome caused by intermittent fasting protect against EAE. Aim 1 will determine how
the gut microbiome modulates local gut immunity and subsequently influences systemic immune responses,
using whole stool transplants from fasting mice to non-fasting mice. The specific protective microbial species
will be identified by isolating the over-represented taxa from intermittently fasting mice and testing their ability
to modulate the local and systemic immune responses. Aim 2 will test the idea that the gut microbiome
protects against EAE by altering leptin and adiponectin production through known pathways controlling their
induction. The study will increase knowledge of the mechanisms in dietary-mediated regulation of EAE/MS
pathogenesis, thereby laying the groundwork for development of novel therapeutic strategies for MS, including
manipulation of the gut microbiome with probiotics and/or prebiotics.

## Key facts

- **NIH application ID:** 10000183
- **Project number:** 5R01NS102633-05
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Yanjiao Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,172
- **Award type:** 5
- **Project period:** 2017-07-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000183

## Citation

> US National Institutes of Health, RePORTER application 10000183, Intermittent Fasting-induced Gut Microbiome Modulation of CNS Autoimmunity (5R01NS102633-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000183. Licensed CC0.

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