# Role of the gut microbiome and inflammation in dietary olfactory loss

> **NIH NIH F31** · FLORIDA STATE UNIVERSITY · 2022 · $41,151

## Abstract

ABSTRACT
Previous experiments in our lab have shown that a fatty diet reduces olfactory sensory neuronal abundance.
Isocaloric feeding in which a fat-fed mouse consumed the same number of calories as a control-fed mouse, but
of fatty chow, prevented obesity but did not prevent the neuronal loss. It appears that the consumption of fat in
the diet induces the observed olfactory changes, not excess adiposity or overconsumption. The physiological
connections between fat consumption and olfactory anatomical and functional changes have not been explored.
The overall objective of this proposal is to uncover the mechanistic link between fatty diet consumption and
olfactory changes. A fatty diet is known to modify gut microbiome composition, often increasing Firmicutes and
Proteobacteria, and decreasing Bacteroidetes. The gut microbiome influences intestinal epithelial structure, and
a high-fat diet compromises intestinal barrier function by reducing tight junction integrity. This allows for
molecules to leak out of the gut and can result in an elevation of circulating lipopolysaccharides (LPS). This
condition is called metabolic endotoxemia and is observed in fat-fed mice. LPS is a component of the outer
membrane of Gram-negative bacteria. LPS is a ligand for the Toll-like receptor 4, and activates immune cells,
induces inflammatory cytokine release, and is used experimentally to induce systemic inflammation. LPS has
been shown to induce neurodegeneration, neuroinflammatory NF-κB signaling, and behavioral changes. This
proposal seeks to probe the connections between a fatty diet, gut microbiome changes, circulating LPS,
neuroinflammation, and olfactory changes through a series of experiments. I hypothesize that the fatty diet
induces changes in the gut microbiome that compromise intestinal integrity, leading to elevated levels of
circulating LPS, which causes chronic neuroinflammation and the subsequent anatomical and behavioral
changes of the olfactory system. First, circulating levels of LPS will be measured in ad libitum fat- and
isocalorically fat-fed mice to determine if they exhibit metabolic endotoxemia. Next, neuroinflammation will be
induced via LPS injection to uncover if this is sufficient to induce olfactory changes. Fecal samples collected
from control-fed, fat-fed ad libitum, and iscalorically fat-fed mice will be sequenced to measure changes in gut
microbiota. Fecal samples from these mice will also be transplanted to control-fed mice to determine if this can
induce olfactory changes. Finally, olfactory tissue will be harvested from control-fed, fat-fed ad libitum, and
isocalorically fat-fed mice to measure neuroinflammation using chromatin immunoprecipitation. Overall, these
experiments will investigate the role of neuroinflammation and the gut microbiome on olfactory sensory neuronal
abundance and odor discrimination to uncover the physiological events linking a fatty diet and olfactory changes.

## Key facts

- **NIH application ID:** 10537558
- **Project number:** 1F31DC019867-01A1
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Ashley Loeven
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,151
- **Award type:** 1
- **Project period:** 2022-08-08 → 2024-08-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537558

## Citation

> US National Institutes of Health, RePORTER application 10537558, Role of the gut microbiome and inflammation in dietary olfactory loss (1F31DC019867-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10537558. Licensed CC0.

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