One‐third of epilepsy patients have drug‐resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut‐brain‐axis are likely to shed light on epilepsy pathogenesis, anti‐seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood‐brain barrier disruption, and altered neuromodulators. High‐throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug‐sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low‐carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted.

中文翻译：

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耐药性癫痫与肠道微生物组之间的交叉对话

三分之一的癫痫患者患有耐药性癫痫 (DRE)，这通常伴有多种药物毒性以及精神和认知合并症。对微生物组和肠脑轴的理解进展可能有助于阐明癫痫发病机制、抗癫痫药物 (ASM) 耐药性和潜在的治疗靶点。肠道菌群失调与炎症、血脑屏障破坏和神经调节剂改变有关。高通量和宏基因组测序促进了微生物物种和功能途径的表征。与药物敏感患者和健康对照相比，DRE 患者的肠道微生物组组成发生了改变。生酮饮食和改良阿特金斯饮食可以减少一些 DRE 患者的癫痫发作。这些低碳水化合物饮食疗法改变了肠道微生物群的分类和功能组成，饮食反应者和非反应者的组成各不相同。小鼠模型表明，特定的门对于从饮食中赋予功效是必要的，而抗生素治疗可能会消除功效。饮食的影响可能涉及微生物群的改变、特定微生物相互作用的促进以及影响癫痫发作的脑神经递质水平的变化。了解饮食如何操纵癫痫发作的机制可能会提示新的治疗方法。大多数 ASM 通过对离子通道和神经递质的影响作用于神经元传递。然而，ASM 也可能通过肠道微生物群来发挥其作用。在动物模型中，微生物群组成（例如，某些门的丰度）可能因 ASM 活性药物代谢物而异。鉴于对 DRE 中肠道微生物组的理解不断加深，益生菌是另一种潜在的治疗方法。益生菌会改变微生物群的组成，小型研究表明，这些补充剂可以减少某些患者的癫痫发作。DRE 对患者和社会产生巨大影响，肠道微生物组有望成为潜在的治疗目标。然而，对于哪些患者可能是反应者的确切机制和识别仍然难以捉摸。有必要进一步研究。DRE 对患者和社会产生巨大影响，肠道微生物组有望成为潜在的治疗目标。然而，对于哪些患者可能是反应者的确切机制和识别仍然难以捉摸。有必要进一步研究。DRE 对患者和社会产生巨大影响，肠道微生物组有望成为潜在的治疗目标。然而，对于哪些患者可能是反应者的确切机制和识别仍然难以捉摸。有必要进一步研究。