Zou Shangnan, Li Yinchao, Zou Qihang, Yang Man, Li Huifeng, Niu Ruili, Lai Huanling, Wang Jiaoyang, Yang Xiaofeng, Zhou Liemin
Clinical Neuroscience Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Front Microbiol. 2024 Jun 19;15:1403892. doi: 10.3389/fmicb.2024.1403892. eCollection 2024.
The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.
We aimed to unravel the intrinsic mechanisms through rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.
We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of and significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, , and showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.
In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.
近年来，肠道微生物群以及微生物群-肠-脑轴受到了广泛关注，成为介导包括癫痫在内的许多中枢神经系统相关疾病发生和发展机制的关键因素。在临床实践中，喹诺酮类抗生素的副作用之一是降低癫痫发作阈值或加重病情。然而，其潜在机制仍不清楚。
我们旨在通过rRNA测序和血清非靶向代谢组学分析来揭示内在机制，以阐明肠道微生物群在环丙沙星诱导的癫痫易感性和毛果芸香碱诱导的癫痫大鼠模型中的作用。
我们观察到环丙沙星治疗增加了癫痫易感性并导致肠道菌群失调。我们还在毛果芸香碱诱导的癫痫大鼠的肠道微生物群中发现了类似的变化。值得注意的是，在环丙沙星诱导的癫痫易感性和毛果芸香碱诱导的癫痫大鼠模型中，[具体物质1]和[具体物质2]的水平均显著升高。然而，[具体物质3]、[具体物质4]和[具体物质5]却出现了相应的降低。此外，血清非靶向代谢组学分析显示，环丙沙星治疗后色氨酸-吲哚代谢产物吲哚-3-丙酸的水平降低，这与毛果芸香碱诱导的癫痫大鼠血浆中的情况相似。重要的是，肠道微生物群、癫痫易感性和吲哚-3-丙酸水平的改变可通过粪便微生物群移植恢复。
总之，我们的研究结果表明，环丙沙星诱导的癫痫易感性部分是由肠道微生物群和色氨酸-吲哚代谢介导的。这些关联可能在癫痫发生中起作用，并影响癫痫的发展进程和治疗结果。
