# Understanding the role of the gut-brain axis in modulating Cadmium neurotoxicity

> **NIH NIH K99** · UNIVERSITY OF WASHINGTON · 2022 · $101,952

## Abstract

PROJECT SUMMARY
 Cadmium (Cd) is a heavy metal with major public health concern around the world. Increasing studies
suggest that Cd is a neurotoxicant, and the Cd exposure is associated with learning and memory deficits, and
various neurodegenerative diseases in humans. My previous study has found that environmental relevant Cd
exposure can impair learning and memory in animals. However, the current knowledge about the mechanisms
of Cd neurotoxicity is still very limited. There is an increasing recognition that the gut-brain axis, a communication
pathway between the central nervous system and the gut microbiome, is important for regulating neurological
functions. Since the gut microbiome is a target of Cd toxicity, I hypothesized that the gut-brain axis
mechanistically contributes to Cd neurotoxicity. This project aims to determine if the gut microbiome contributes
to Cd neurotoxicity on learning and memory and identify specific microbiomes and microbial metabolites that
mechanistically contribute to Cd neurotoxicity. The K99 mentored phase proposes to (1) examine the changes
of the gut microbiome and microbial metabolites according to the onset of Cd-induced learning and memory
deficits, and further (2) determine if the gut microbiome is both necessary and sufficient for Cd neurotoxicity by
using antibiotics-treated mice to determine how depletion of the gut microbiome modulates the Cd-induced
learning and memory deficits in mice, and conducting fecal microbiota transplant in antibiotics-treated mice
inoculated with intestinal content collected from Cd-treated mice with impaired memory to determine how a
“diseased microbiome” itself contributes to cognitive deficits. During this time, the candidate will complete
mentored training and courses in the microbiome, bioinformatics, second-generation sequencing, and other
professional development training in preparation for the independent R00 phase. In the independent phase, with
the findings from the K99 phase, this project will further identify specific microbiomes and microbial neuroactive
metabolites that contribute to Cd toxicity in learning and memory. Regarding the expected outcomes, this project
will determine for the first time the importance of the gut-brain axis in Cd-induced neurotoxicity, enhance the
understanding of the mechanisms concerning the neurotoxicity of Cd and other environmental neurotoxicants,
and provide translational insights for the design of prevention and intervention strategies to mitigate Cd
neurotoxicity by reprogramming the gut microbiome.

## Key facts

- **NIH application ID:** 10427554
- **Project number:** 1K99ES034068-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Hao Wang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $101,952
- **Award type:** 1
- **Project period:** 2022-09-09 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427554

## Citation

> US National Institutes of Health, RePORTER application 10427554, Understanding the role of the gut-brain axis in modulating Cadmium neurotoxicity (1K99ES034068-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10427554. Licensed CC0.

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