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Updated: Aug 9, 2025
Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Tebuconazole mediates cognitive impairment via the microbe-gut-brain axis (MGBA) in mice
Tingting Ku1, Yutong Liu1, Yuanyuan Xie1
1College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, China.
Abstract:
Tebuconazole, one of the most widely used triazole fungicides, is reported to potentially pose a risk of inducing neurological disorders in human beings. Considering the increasing exposure, whether it could influence cognitive function remains to be elucidated. Herein, we used a mouse model to evaluate the potential cognitive risks and possible mechanisms from the continuous edible application of tebuconazole at low concentrations. Our study revealed that tebuconazole deteriorated spatial learning and memory and downregulated the expression of glutamate receptor subunits. Importantly, metagenomic analysis indicated that tebuconazole not only led to significant shifts in the composition and diversity of the gut microbiota but also changed intestinal homeostasis. Specifically, after exposure, tebuconazole circulated in the bloodstream and largely entered the gut-brain axis for disruption, including disturbing the Firmicutes/Bacteroidetes ratio, interrelated neurotransmitters and systemic immune factors. Moreover, pretreatment with probiotics improved immune factor expression and restored the deterioration of synaptic function and spatial learning and memory. The current study provides novel insights concerning perturbations of the gut microbiome and its functions as a potential new mechanism by which tebuconazole exposes cognitive function-related human health.
Insights
This study shows the fungicide tebuconazole harms cognitive function by disrupting the gut microbiome and gut-brain axis in mice. Probiotic treatment offers a potential protective strategy against these neurotoxic effects.
Area of Science:
- Neuroscience
- Toxicology
- Microbiology
Background:
- Tebuconazole is a widely used fungicide with potential neurotoxic risks.
- Its impact on cognitive function and underlying mechanisms, especially concerning gut-brain axis disruption, requires further investigation.
Purpose of the Study:
- To evaluate the cognitive risks associated with low-dose tebuconazole exposure.
- To elucidate the mechanisms, including gut microbiota and gut-brain axis alterations, underlying tebuconazole's neurotoxicity.
Main Methods:
- A mouse model was used to assess cognitive function after continuous low-dose tebuconazole administration.
- Metagenomic analysis was employed to study gut microbiota composition and diversity.
- Changes in gut-brain axis components, including neurotransmitters and immune factors, were analyzed.
Main Results:
- Tebuconazole exposure impaired spatial learning and memory and reduced glutamate receptor expression.
- Significant alterations in gut microbiota composition, diversity, and intestinal homeostasis were observed.
- Tebuconazole disrupted the gut-brain axis by altering the Firmicutes/Bacteroidetes ratio, neurotransmitters, and systemic immune factors.
Conclusions:
- Tebuconazole exposure negatively impacts cognitive function through gut microbiome dysbiosis and gut-brain axis disruption.
- Probiotic pretreatment demonstrated a protective effect, improving immune function and restoring cognitive performance.
- Gut microbiome perturbations represent a potential mechanism linking tebuconazole exposure to cognitive health risks.
