Topiramate alters the gut microbiome to aid in its anti-seizure effect.
Topiramate alters the gut microbiome to aid in its anti-seizure effect.
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DOI：
10.3389/fmicb.2023.1242856
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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人们对肠道微生物群在癫痫中的作用越来越感兴趣，然而，目前尚不清楚抗癫痫药物（ASM）是否在肠-脑轴中发挥作用。为了测试这一点，我们研究了ASM托吡酯对小鼠肠道微生物组的影响。将托吡酯溶于C57 BL/6 J小鼠的饮用水中给药5周。对5周时收集的粪便样品进行16 S核糖体RNA基因测序。进行α多样性、β多样性和差异丰度分析。分析盲肠内容物的短链脂肪酸（SCFA）组成。在盐水、托吡酯、约氏乳杆菌以及托吡酯和约氏乳杆菌处理的小鼠中进行戊四唑（PTZ）点燃。小鼠每隔一天接受PTZ注射，共注射12次，视频监测癫痫发作活动30分钟并评分。我们的研究表明，托吡酯摄入显著增加了幼稚小鼠肠道微生物组中的约氏乳杆菌。托吡酯和约氏乳杆菌联合治疗（但不是单独治疗）可降低PTZ诱导癫痫发作的易感性。共处理也显着增加了丁酸的百分比和丰富的丁酸生产家庭毛螺菌科在肠道中，并提高了GABA/谷氨酸的比例在皮层。我们的研究结果表明，ASM可以改变肠道微生物组，以帮助其在体内的抗癫痫作用，并表明益生菌约氏乳杆菌作为托吡酯的辅助治疗在降低癫痫易感性方面的潜力。
There is a growing interest in the role of the gut microbiota in epilepsy, however, it is unclear if anti-seizure medications (ASMs) play a role in the gut-brain axis. To test this, we investigated the impact of the ASM topiramate on the gut microbiome of mice. C57BL/6J mice were administered topiramate in their drinking water for 5 weeks. 16S ribosomal RNA gene sequencing was performed on fecal samples collected at 5 weeks. Analysis of alpha diversity, beta diversity, and differential abundance were performed. Cecal contents were analyzed for short-chain fatty acids (SCFAs) composition. Pentylenetetrazol (PTZ)-kindling was performed in saline, topiramate, Lactobacillus johnsonii, and topiramate and Lactobacillus johnsonii treated mice. Mice received PTZ injection every other day for a total of twelve injections, seizure activity was video monitored for 30 minutes and scored. Our study revealed that topiramate ingestion significantly increased Lactobacillus johnsonii in the gut microbiome of naïve mice. Treatment with topiramate and Lactobacillus johnsonii together, but not alone, reduced susceptibility to PTZ-induced seizures. Co-treatment also significantly increased the percent of butyrate and the abundance of butyrate-producing family Lachnospiraceae in the gut, and elevated the GABA/glutamate ratio in the cortex. Our results demonstrate that an ASM can alter the gut microbiome to aid in their anti-seizure effect in vivo and suggest the potential of the probiotic Lactobacillus johnsonii as an adjunct therapy with topiramate in reducing seizure susceptibility.
影响因子：
5.6
作者：
通讯作者：
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