- 2025-12
- International dental journal 75(6)
Study Design
- Population
- C57BL/6 mice
- Methods
- Murine model: first molars extracted, followed by metagenomic sequencing, metabolomics, and transcriptomics of fecal, serum, and brain tissue; pro-inflammatory markers assessed; neurotoxic effects of L-Asparagine validated using HT22 neuronal cell models.
- Funding
- Unclear
Introduction and aims
Tooth loss is not only a dental issue but also affects gut microbial composition and downstream physiological responses. This study investigates how tooth loss-induced alterations in the gut microbiota influence metabolic and neural function. This study aimed to elucidate the mechanistic links between microbiota dysbiosis, metabolic imbalance, and neuroinflammation following tooth loss.Methods
Using a murine model, the first molars of C57BL/6 mice were extracted, followed by the collection of fecal samples, serum, and brain tissue for subsequent metagenomic sequencing, metabolomics, and transcriptomics. Pro-inflammatory markers (IL-6, TNF-α) and PSD95 expression were assessed. The neurotoxic effects of key metabolite L-Asparagine were validated using HT22 neuronal cell models.Results
Tooth loss induced gut microbiota dysbiosis, which subsequently mediated pathological alterations in brain tissue, characterised by a reduction in beneficial Butyribacter and an increase in pathogenic taxa. Corresponding shifts in systemic metabolism were observed, along with changes in brain gene expression, particularly in genes related to neuroinflammation. In vitro experiments further demonstrated that L-Asparagine directly induced neurotoxicity in HT22 hippocampal neurons through ROS overproduction, apoptosis, and inflammatory activation.Conclusion
Tooth loss induced gut microbiota dysbiosis, systemic metabolic disruptions, and neuroinflammatory responses. Our findings demonstrated that tooth loss exacerbated neuroinflammation via gut-derived L-Asparagine, providing a mechanistic link in the oral-gut-brain axis.Clinical relevance
This study demonstrated that molar extraction in mice disrupted gut microbiota and promoted neuroinflammation via L-Asparagine, suggesting that maintaining oral integrity might help preserve neurological health. This could open new avenues for microbiota-targeted interventions in neurodegenerative disease prevention.
Research Insights
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