Laboratory of Cellular and Molecular Biology (LBCM), Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió, AL, 57072-900, Brazil.
Laboratory of Molecular Diversity (LDM), Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió, AL, 57072-900, Brazil.
Mol Neurobiol. 2022 Oct;59(10):6429-6446. doi: 10.1007/s12035-022-02984-3. Epub 2022 Aug 13.
Evidence supports that the gut microbiota and bacteria-dependent metabolites influence the maintenance of epileptic brain activity. However, the alterations in the gut microbiota between epileptic versus healthy individuals are poorly understood. We used a multi-omic approach to evaluate the changes in the composition of gut metagenome as well in the fecal metabolomic profile in rats before and after being submitted to status epilepticus (SE)-induced temporal lobe epilepsy (TLE). The 16S ribosomal RNA (rRNA) sequencing of fecal samples coupled to bioinformatic analysis revealed taxonomic, compositional, and functional shifts in epileptic rats. The species richness (Chao1 index) was significantly lower in the post-TLE group, and the β-diversity analysis revealed clustering separated from the pre-TLE group. The taxonomic abundance analysis showed a significant increase of phylum Desulfobacterota and a decrease of Patescibacteria in the post-TLE group. The DESEq2 and LEfSe analysis resulted in 18 genera significantly enriched between post-TLE and pre-TLE groups at the genus level. We observed that epileptic rats present a peculiar metabolic phenotype, including a lower concentration of D-glucose and L-lactic acid and a higher concentration of L-glutamic acid and glycine. The microbiota-host metabolic correlation analysis showed that the genera differentially abundant in post-TLE rats are associated with the altered metabolites, especially the proinflammatory Desulfovibrio and Marvinbryantia, which were enriched in epileptic animals and positively correlated with these excitatory neurotransmitters and carbohydrate metabolites. Therefore, our data revealed a correlation between dysbacteriosis in epileptic animals and fecal metabolites that are known to be relevant for maintaining epileptic brain activity by enhancing chronic inflammation, an excitatory-inhibitory imbalance, and/or a metabolic disturbance. These data are promising and suggest that targeting the gut microbiota could provide a novel avenue for preventing and treating acquired epilepsy. However, the causal relationship between these microbial/metabolite components and the SRS occurrence still needs further exploration.
有证据表明，肠道微生物群和细菌依赖性代谢物会影响致痫性大脑活动的维持。然而，目前尚不清楚癫痫患者与健康个体之间肠道微生物群的改变。我们使用多组学方法评估了经历癫痫持续状态（SE）诱导的颞叶癫痫（TLE）前后大鼠肠道宏基因组组成和粪便代谢组学特征的变化。粪便样本的 16S 核糖体 RNA（rRNA）测序结合生物信息学分析显示，癫痫大鼠的分类、组成和功能发生了变化。TLE 后组的物种丰富度（Chao1 指数）显著降低，β多样性分析显示聚类与 TLE 前组分离。分类丰度分析显示，TLE 后组厚壁菌门的丰度显著增加，Patescibacteria 的丰度显著降低。DESEq2 和 LEfSe 分析结果表明，在属水平上，TLE 后组和 TLE 前组之间有 18 个属显著富集。我们观察到癫痫大鼠表现出一种特殊的代谢表型，包括 D-葡萄糖和 L-乳酸浓度降低，L-谷氨酸和甘氨酸浓度升高。微生物群-宿主代谢相关性分析表明，TLE 后大鼠中丰度差异较大的属与代谢物改变有关，特别是促炎的脱硫弧菌和马文氏菌，它们在癫痫动物中富集，并与这些兴奋性神经递质和碳水化合物代谢物呈正相关。因此，我们的数据揭示了癫痫动物的肠道菌群失调与粪便代谢物之间的相关性，这些代谢物已知通过增强慢性炎症、兴奋-抑制失衡和/或代谢紊乱与维持癫痫性大脑活动有关。这些数据很有前景，表明靶向肠道微生物群可能为预防和治疗获得性癫痫提供新途径。然而，这些微生物/代谢物成分与 SRS 发生之间的因果关系仍需要进一步探索。
