# Gut-brain axis in Alzheimer's disease: translational 7T MRI markers and underlying mechanisms

> **NIH NIH R56** · UNIVERSITY OF MISSOURI-COLUMBIA · 2024 · $797,809

## Abstract

Project Summary
Alzheimer’s disease (AD) is the most common form of dementia with hallmarks of extracellular beta amyloid
(Aβ) plaques (A), intraneuronal tau tangles (T), and neurodegeneration (N), known as the A/T/N framework, a
descriptive classification for AD biomarkers. Accumulating evidence shows that a severely imbalanced
microbial community, or dysbiosis, is associated with A/T/N and neuroinflammation in AD patients compared
with healthy controls (HC). However, it remains unknown how individual microbiota correlates with regional
A/T/N neuroimaging markers in AD and HC. It is also unknown if dysbiosis directly promotes and accelerates
A/T/N at early stage and whether there are effective interventions available to mitigate the dysbiosis and thus
AD risk. Therefore, the goal of the project is to design a translational study, employing parallel human and
preclinical animal experiments to understand mechanism and identify interventions for filling these knowledge
gaps. The central hypothesis is that severity of dysbiosis between AD and HC individuals will correlate with
their regional A/T/N imaging markers and cognitive status; young healthy triple transgenic AD (3xTg-AD) mice
received fecal microbiome transplantation (FMT) from AD patients (FMT-AD) will have reproduced dysbiosis as
the donors, which will accelerate A/T/N, neuroinflammation and cognitive impairment of the mice. Interventions
with inducible nitric oxide synthase (iNOS) inhibition will mitigate A/T/N and neuroinflammation, and prebiotic
diet (inulin) supplementation can further restore microbiome balance to protect brain physiology and cognition.
The central hypothesis will be tested by the following three Specific Aims: (1) Identify correlation of dysbiosis,
A/T/N imaging markers and cognition in humans; (2) Reveal impact of iNOS on mitigating A/T/N in the
presence of dysbiosis; (3) Determine ability of inulin, with and without functional iNOS, to rescue FMT-AD-
induced A/T/N and cognitive impairment. Participants who had PET scans for “A/T” will be recruited for the
study, and ultrahigh resolution 7T MRI will be used to determine “N”. Translational 7T MRI, gut microbiome
sequencing and cognitive assessments will be applied to both humans and mice to determine longitudinal
effects of gut-brain interactions. A novel iNOS knockout triple transgenic AD (iNOS-KO/3xTg-AD) mouse
model has been created for the project to study the iNOS effects on mitigating A/T/N despite of gut dysbiosis.
Biochemical assays and brain staining will be used to determine “A/T” in the mice. Inflammatory gene
expression will be identified by transcriptomics. It is anticipated that the findings from this study will have
tremendous positive impact as they will enhance the understanding of gut-brain interactions underlying A/T/N
in AD and pave the way for future disease-modifying interventions for AD via the microbiome-gut-brain axis. As
iNOS inhibitors, inulin diet, 7T MRI and microbiome analyses are availa...

## Key facts

- **NIH application ID:** 10924050
- **Project number:** 5R56AG079586-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Priti Balchandani
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $797,809
- **Award type:** 5
- **Project period:** 2023-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924050

## Citation

> US National Institutes of Health, RePORTER application 10924050, Gut-brain axis in Alzheimer's disease: translational 7T MRI markers and underlying mechanisms (5R56AG079586-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10924050. Licensed CC0.

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