# Functional Microbiomics, Inflammation and Pathogenicity

> **NIH NIH P20** · UNIVERSITY OF LOUISVILLE · 2020 · $345,003

## Abstract

Abstract
Alzheimer’s disease (AD) is a degenerative disease of the brain associated with aging which is responsible for
profound morbidity and mortality. Ninety-nine percent of cases are of unknown cause, and not created by an
abnormal gene. The disease progressively affects memory, judgment, abstraction, perception, visual-spatial
abilities and language as well as other functions. There is also sterile inflammation of brain associated with
the progression of AD. The microbiota is being extensively studied and has been found to be critically important
for health and disease. The role of the microbiota in AD is suggested by the early onset of olfactory dysfunction
in the disease as well as many other studies that document changes in microbiota associated with ageing and
AD progression. Such microbiota changes are also observed in mouse models, yet no clear candidate microbes
for promoting or delaying AD have been identified. We have established a Functional Microbiomics Core (FMC)
at UofL that supports the work of many faculty by providing germ-free, gnotobiotic mice as well as anaerobic
culturing and characterization of microbiota signatures by 16S sequencing. In this administrative supplement,
we propose to expand the FMC to include AD mouse models. We will rederive the well-established AD models
APP/PS1 and 3XTg-AD and maintain these as germ-free and test them in behavioral models. We will examine
the role of bacterial amyloids in seeding the brain AB by using the E.Coli strains expressing the amyloid protein
curli. In Aim2, we will recolonize the germ-free APP/PS1 mice with AD or control stool samples to generate stable
humanized microbiota mice that will serve as models for examining the promoting and protective roles of specific
microbiota populations in AD. This work has important implications for all neurological conditions involving
misfolded proteins and microbiota. The approaches outlined here will be highly productive and rewarding both
interms of understanding disease mechanisms and developing novel preventive/therapeutic strategies.

## Key facts

- **NIH application ID:** 10123408
- **Project number:** 3P20GM125504-03S1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Richard J Lamont
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,003
- **Award type:** 3
- **Project period:** 2020-06-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123408

## Citation

> US National Institutes of Health, RePORTER application 10123408, Functional Microbiomics, Inflammation and Pathogenicity (3P20GM125504-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10123408. Licensed CC0.

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