# Metabolic control of gut-brain axis in Familial Dysautonomia

> **NIH NIH R01** · MONTANA STATE UNIVERSITY - BOZEMAN · 2021 · $580,528

## Abstract

Project Summary
The goal of this project is to determine whether metabolism and the gut microbiome underlie
hallmark features of the neurodegenerative disease, Familial Dysautonomia (FD). While clinical
hallmarks of FD involve the sensory and autonomic nervous system, including cardiovascular
instability and orthostatic hypotension with bouts of hypertension, another cardinal feature is
impaired gastrointestinal (GI) tract motility. The human GI tract is regulated by over 500 million
intrinsic neurons, called the Enteric Nervous system (ENS). The ENS is a component of the
Autonomic Nervous System and has been shown to be severely reduced in neuronal number in
FD patients. Furthermore, FD patients and mouse models for FD are underweight and mice are
essentially devoid of subcutaneous white adipose tissue. The underlying etiology for their reduced
mass is not known but recent data has shown that mitochondrial function is impaired in FD
patients and mice. The “gut” and “brain” communicate extensively and accumulating data
demonstrate the strong role the gut microbiome exerts on both metabolism and the nervous
system, resulting in exacerbation of neurodegenerative disorders. We hypothesize that FD
patients and mice are underweight because they suffer from a global metabolic syndrome induced
by a combination of gut microbiome alteration, impaired energy homeostasis and mitochondrial
dysfunction, and reduced gut regulation by the enteric, autonomic and sensory nervous systems.
Using a multi-disciplinary approach, we will analyze the gut microbiome and metabolome of FD
patients and manipulate these systems in mouse models of FD to identify and sort causal
mechanisms mediating both metabolic impairments and neuronal health. Although specifically
focused on FD, our results will broadly apply to other neurodegenerative diseases, where
metabolism and the microbiome are thought to play a role.

## Key facts

- **NIH application ID:** 10163176
- **Project number:** 5R01DK117473-04
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** VALERIE COPIE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $580,528
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163176

## Citation

> US National Institutes of Health, RePORTER application 10163176, Metabolic control of gut-brain axis in Familial Dysautonomia (5R01DK117473-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163176. Licensed CC0.

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