# Deciphering the effect of human microbiota on Alzheimer's disease using C. elegans models of protein conformational diseases

> **NIH NIH R03** · UNIVERSITY OF FLORIDA · 2022 · $76,250

## Abstract

Alzheimer’s disease (AD) is a fatal neurodegenerative disorder characterized by a progressive loss of
memory and cognitive function due to protein misfolding and aggregation, a common feature among protein
conformational diseases (PCDs). The exact factors that influence PCDs are not known; however, recent
evidence suggests that bacteria may contribute to the pathogenesis of AD and other neurodegenerative
diseases. To better understand the influence of bacteria on protein homeostasis (proteostasis), we are studying
the effects of bacterial colonization of the Caenorhabditis elegans gut on protein aggregation in the intestine and
other tissues.
 In a pilot screen of over 60 strains, we identified bacteria that can either increase or decrease protein
aggregation not only in the intestine but throughout other tissues, including muscle, neurons, and gonad. We
found that the bacteria that suppress protein aggregation have something in common—they produce butyrate.
In follow-up experiments, we demonstrated that both exogenous and endogenous butyrate suppressed bacteria-
mediated protein aggregation. These results suggest that intestinal bacteria affect host proteostasis and can
potentially contribute to the pathogenesis of AD. Collectively, our preliminary data reveal a possible causative
role for bacteria in diseases that are characterized by protein aggregation. As such, we propose to further
investigate the effect of bacteria on proteostasis using C. elegans models by: (I) determining the impact of
intestinal colonization by all human microbiome bacterial isolates on host proteostasis and pathogenesis of AD,
and (II) observing the effect of exogenous and endogenous butyrate on bacteria that enhance protein
aggregation. Deciphering the effect that bacteria have on host proteostasis will ultimately provide a basis for the
development of prophylactics, therapeutics, and biomarkers.

## Key facts

- **NIH application ID:** 10341111
- **Project number:** 5R03AG070580-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Daniel Milosz Czyz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $76,250
- **Award type:** 5
- **Project period:** 2021-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10341111

## Citation

> US National Institutes of Health, RePORTER application 10341111, Deciphering the effect of human microbiota on Alzheimer's disease using C. elegans models of protein conformational diseases (5R03AG070580-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10341111. Licensed CC0.

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