# Supplement to Prebiotics Intervention to Reduce Alzheimer's Disease Risk via Brain-Gut Axis in an APOE4 Mouse Model

> **NIH NIH RF1** · UNIVERSITY OF KENTUCKY · 2020 · $152,916

## Abstract

Project Summary
Traumatic brain injury (TBI) currently affects 1.6-3.8 million people in the US annually. Over the past 30 years,
research has linked TBI to a greater risk of developing Alzheimer’s disease (AD) or another dementia years
after the original head injury. More recently, emerging evidence shows that TBI increases intestinal
permeability and alters gut microbiome composition that further exacerbate inflammation, brain
vascular/metabolic dysfunctions and perpetuate long-term secondary sequelae. Therefore, the presumption is
that having a pre-existing healthy gut microbiome composition/diversity may be critical for protecting brain
functions after TBI and potentially prevent the further development of cognitive impairment. In this study, our
goal is to determine if AD risk can be reduced by administrating prebiotic Inulin diet before TBI in young mice
to protect the brain vascular, metabolic, and white matter (WM) integrity and reduce neuroinflammation through
gut microbiome modulation. The central hypothesis is that mice with inulin diet before TBI will have healthier
gut microbiome profile and better protection for brain vascular, metabolic and WM integrity after TBI, and thus
protect the cognitive function. We will test the hypothesis by pursuing the following two Specific Aims: (i)
Determine Inulin effects on the gut microbiome and SCFAs production for protecting TBI; (ii) Identify Inulin
effects on brain functions and neuroinflammation for protecting TBI. This project is innovative because it is one
of the first studies to identify the protective effects of prebiotic Inulin for TBI via gut-brain axis. It is also
innovative because it challenges the current standing of the field of TBI. Instead of trying to reduce the
neurological and systemic effects of injury after it occurs, we shift the focus to mitigation of the injury cascade
in populations already known to be at risk such as military personnel and athletes. The success of the study
would enhance our understanding of CNS-peripheral interactions in TBI, and identify potential effective dietary
intervention for preventing AD in a younger population. As Inulin-related diets are commercially available, and
MRI neuroimaging and gut microbiome analyses are readily to be used for humans, our approaches are highly
translational; if we are able to show that we can use diet as a measure to mitigate secondary sequelae in mice,
we’d be able to rapidly transition to studies with humans.

## Key facts

- **NIH application ID:** 10140944
- **Project number:** 3RF1AG062480-01S1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ai-Ling Lin
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $152,916
- **Award type:** 3
- **Project period:** 2019-05-01 → 2021-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140944

## Citation

> US National Institutes of Health, RePORTER application 10140944, Supplement to Prebiotics Intervention to Reduce Alzheimer's Disease Risk via Brain-Gut Axis in an APOE4 Mouse Model (3RF1AG062480-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10140944. Licensed CC0.

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