# Project 3 - Mechanistic studies on role of gut microbiome in models for Alzheimer's disease

> **NIH NIH U19** · DUKE UNIVERSITY · 2020 · $430,206

## Abstract

ABSTRACT – PROJECT 3
Sensory and molecular signals from the environment influence brain activity and help shape psychological or
physical responses. The gastrointestinal (GI) tract represents our largest portal to the molecular world around
us, and sends signals that travel to all organs of the body that impact their function, including the brain.
Conduits used for gut-to-brain communication include, among others, metabolites produced in the gut that may
activate the enteric nervous system (ENS) and signal via the vagus nerve, or molecules may even reach the
brain through systemic circulation. However, there is remarkably little known about the cellular and molecular
mechanisms that connect the gut to the brain. Further, if indeed the flow of complex signals from the gut
modulates brain activity, perhaps changes due to altered environments may result in deviations from brain
health. Humans share an intimate and life-long association with multitudes of resident microbial species,
known as the microbiome, which represents a potentially strong environmental factor in may diseases. Gut
bacteria regulate nutrition and metabolism, and orchestrate the development and function of the immune
system. Intriguingly, the community structure and composition of the gut microbiome is altered in neurologic
conditions such as anxiety, depression, autism spectrum disorder (ASD), schizophrenia, Parkinson’s disease
(PD) and Alzheimer’s disease (AD). Whether these changes are a consequence of disease or a contributor
remain entirely unknown. Studies that distinguish correlation from causation are both challenging and
unjustified in humans. Thus, we propose to study the functional contributions of the human microbiome in
novel mouse models of AD to test the hypothesis that microbial signals that travel from the gut to the brain
promote neuroimmune activation, pathology, and symptoms of neurodegeneration. While basic and clinical
research is rapidly defining the pathophysiology of AD, the cause(s) of most cases remain unknown. Thus,
even the best medicines, which are relatively ineffective or have severe side effects, only address symptoms
and are not disease-modifying. We provide seminal evidence that the gut microbiome is a key contributor to
the pathology of AD using mouse models, offering entirely novel perspectives into disease etiology. Unraveling
gut-microbiome-brain connections holds the promise of transforming the neurosciences and revealing
potentially revolutionary diagnostics and treatments for Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10017880
- **Project number:** 5U19AG063744-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Rima F Kaddurah-Daouk
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $430,206
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017880

## Citation

> US National Institutes of Health, RePORTER application 10017880, Project 3 - Mechanistic studies on role of gut microbiome in models for Alzheimer's disease (5U19AG063744-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10017880. Licensed CC0.

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