Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, China.
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan 611730, China.
Microb Pathog. 2022 Jan;162:105340. doi: 10.1016/j.micpath.2021.105340. Epub 2021 Dec 6.
Growing evidence implicates the potential effect of microbiota on the pathogenesis and course of epilepsy. However, the effects of valproate (VPA), a broad spectrum anti-epileptic drugs, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in patients with epilepsy treated with valproate.
A total of 10 participants, who were newly diagnosed of cryptogenic epilepsy with treatment naïve and received 1000 mg daily doses of VPA, were recruited in our prospective study. Microbiota compositions were evaluated at baseline and after three months of VPA treatment using 16S rDNA sequencing.
VPA treatment was associated with clinical improvements in all patients, but not changes in gut microbiota richness and complexity (Shannon: p = 0.82). Microbiome composition structure differences also revealed no statistical difference in dissimilarity (Adonis: p = 0.90). No statistical difference taxa were found between two groups. However, the ratio of phyla Firmicutes to Bacteriodetes (ANOVA: p = 0.037) markedly raised after three months of VPA-treatment. A correlation matrix based on the spearman correlation distance confirmed associations between specific fecal taxa and VPA-related clinical metabolic parameters, including drug concentration in the blood, total cholesterol, triglyceride, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and weight gain. (p < 0.05) CONCLUSIONS: Among those patients treated with VPA, characterization of the gut microbiota altered, and gut microbiota associated with weight gain and clinical biochemical indexes, suggesting that microbiome composition data might involve in the mechanisms of VPA induced metabolic disorder.
越来越多的证据表明，微生物群可能对癫痫的发病机制和病程有影响。然而，在人类中，尚未研究广泛使用的抗癫痫药物丙戊酸（VPA）对肠道微生物群的影响。本研究旨在分析接受丙戊酸治疗的癫痫患者的粪便微生物群。
我们的前瞻性研究共招募了 10 名新诊断为隐源性癫痫且未接受治疗且每日接受 1000mg VPA 治疗的患者。在基线时和 VPA 治疗三个月后，使用 16S rDNA 测序评估微生物群组成。
VPA 治疗与所有患者的临床改善相关，但与肠道微生物群丰富度和复杂性无变化相关（Shannon：p=0.82）。在不相似性方面，微生物组组成结构差异也没有统计学差异（Adonis：p=0.90）。两组之间未发现统计学差异的分类群。然而，在 VPA 治疗三个月后，厚壁菌门与拟杆菌门的比例（ANOVA：p=0.037）显著升高。基于 Spearman 相关距离的相关矩阵证实了特定粪便分类群与 VPA 相关临床代谢参数之间的关联，包括血药浓度、总胆固醇、甘油三酯、乳酸脱氢酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶和体重增加。（p<0.05）。
在接受 VPA 治疗的患者中，肠道微生物群的特征发生了改变，与体重增加和临床生化指标相关，提示微生物组组成数据可能涉及 VPA 诱导代谢紊乱的机制。
