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Published on: September 19, 2019
Ciprofloxacin-induced microbiota dysbiosis triggers seizure susceptibility through the microbiota-gut-brain axis
Qihang Zou1,2, Yaqian Zhang1, Shangnan Zou1,3
1Clinical Neuroscience Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Background:
Epilepsy is linked to inflammation and gut microbiota dysbiosis. Ciprofloxacin-induced microbiota disruption may increase seizure susceptibility. This study investigates underlying mechanisms and the therapeutic potential of fecal microbiota transplantation (FMT).
Methods:
A total of 64 male Sprague-Dawley rats were categorized into four experimental groups: Control (CTRL), Ciprofloxacin-treated (CPF), CPF with fecal microbiota transplantation (CPF-FMT), and CPF with phosphate-buffered saline (CPF-PBS). Gut microbiota dysbiosis was induced with ciprofloxacin for 14 days, followed by either FMT or PBS for 14 days. Seizure susceptibility was assessed using pentylenetetrazole (PTZ), alongside molecular analyses of gut and blood-brain barrier integrity, neuroinflammatory markers, and cortical transcriptomics.
Results:
Microbiota dysbiosis was associated with increased seizure susceptibility, accompanied by disruption of intestinal and blood-brain barrier (BBB) integrity, thereby exacerbating systemic and neuroinflammation. Dysbiotic rats exhibited significant reductions in microbial diversity and depletion of protective taxa, including f_Muribaculaceae, f_Prevotellaceae, and Lachnospiraceae_NK4A136_group, which correlated with intestinal barrier dysfunction. This dysfunction was associated with reduced tight junction proteins (ZO-1, Occludin, Claudin-5) and inflammatory cell infiltration. Systemic inflammation and disrupted blood-brain barrier integrity resulted in microglial activation and astrocytic proliferation in the brain. Notably, FMT was related to restoration of microbial diversity, improvement of barrier-related markers, attenuation of neuroinflammatory responses, and a reduction in seizure susceptibility.
Conclusion:
This study provides evidence linking gut microbiota dysbiosis to seizure susceptibility through neuroinflammatory processes, contributing to the understanding of gut-brain axis involvement in fluoroquinolone-induced seizures.
Insights
Gut microbiota disruption increases seizure risk by causing inflammation and damaging barriers. Fecal microbiota transplantation (FMT) can restore gut health, reduce inflammation, and decrease seizure susceptibility in rats.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Epilepsy is associated with inflammation and gut microbiota dysbiosis.
- Disruption of gut microbiota by ciprofloxacin may heighten seizure susceptibility.
- This study explores the mechanisms and therapeutic potential of fecal microbiota transplantation (FMT) for fluoroquinolone-induced seizures.
Purpose of the Study:
- Investigate the link between gut microbiota dysbiosis and seizure susceptibility.
- Elucidate the role of intestinal and blood-brain barrier (BBB) integrity in neuroinflammation.
- Evaluate the efficacy of FMT in mitigating seizure susceptibility and associated pathologies.
Main Methods:
- Utilized a rat model with ciprofloxacin-induced gut dysbiosis.
- Administered FMT or phosphate-buffered saline (PBS) to assess therapeutic effects.
- Assessed seizure susceptibility via pentylenetetrazole (PTZ) challenge and analyzed gut/BBB integrity, neuroinflammation, and cortical gene expression.
Main Results:
- Ciprofloxacin-induced dysbiosis increased seizure susceptibility, gut and BBB dysfunction, and neuroinflammation.
- Reduced microbial diversity and depletion of specific taxa correlated with intestinal barrier defects.
- FMT treatment restored microbial diversity, improved barrier function, reduced neuroinflammation, and decreased seizure susceptibility.
Conclusions:
- Gut microbiota dysbiosis contributes to seizure susceptibility via neuroinflammatory pathways.
- This research highlights the gut-brain axis's role in fluoroquinolone-induced seizures.
- Fecal microbiota transplantation shows promise as a therapeutic strategy for managing seizures linked to gut dysbiosis.
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