■近年来,肠道微生物群和微生物群-肠道-大脑轴受到了广泛关注,在调节许多中枢神经系统相关疾病的发生和发展的机制中,包括癫痫。在临床实践中,喹诺酮类抗生素的副作用之一是癫痫发作阈值降低或加重。然而,潜在机制尚不清楚.
■我们旨在通过16SrRNA测序和血清非靶向代谢组学分析来阐明内在机制,以阐明肠道微生物群在环丙沙星诱导的癫痫易感性和锂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发作易感性并引起肠道生态失调。我们还发现锂毛果芸香碱诱导的癫痫大鼠的肠道菌群发生了类似的变化。值得注意的是,在环丙沙星诱导的癫痫发作易感性和锂毛果芸香碱诱导的癫痫大鼠模型中,Akkermansia和拟杆菌的水平均显著升高.然而,Marvinbryantia,镰刀菌,和Ruminococycaceae_NK4A214_组显示出巧合的减少。此外,血清非靶向代谢组学分析显示吲哚-3-丙酸水平降低,色氨酸-吲哚代谢的产物,环丙沙星治疗后,与锂毛果芸香碱诱导的大鼠癫痫血浆中的那些相似。重要的是,肠道微生物群的改变,癫痫发作易感性,和吲哚-3-丙酸水平可以通过粪便微生物移植来恢复。
■总之,我们的研究结果提供了证据,证明环丙沙星诱发的癫痫发作易感性部分是由肠道菌群和色氨酸-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。
UNASSIGNED: 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.
UNASSIGNED: We aimed to unravel the intrinsic mechanisms through 16S 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.
UNASSIGNED: 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 Akkermansia and Bacteroides significantly increased in both the
ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group 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.
UNASSIGNED: 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.