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癫痫中的微生物群-肠道-脑轴:基于实验室证据的药物治疗靶点及其潜在的临床应用

The microbiome-gut-brain axis in epilepsy: pharmacotherapeutic target from bench evidence for potential bedside applications.

作者信息

Kundu Snehashis, Nayak Sudipta, Rakshit Debarati, Singh Tanveer, Shukla Rahul, Khatri Dharmendra Kumar, Mishra Awanish

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India.

Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas, USA.

出版信息

Eur J Neurol. 2023 Nov;30(11):3557-3567. doi: 10.1111/ene.15767. Epub 2023 Mar 22.

Abstract

The gut-brain axis augments the bidirectional communication between the gut and brain and modulates gut homeostasis and the central nervous system through the hypothalamic-pituitary-adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. Preclinical and clinical reports showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis, and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy. Advanced consideration of the gut-microbiota-brain axis can reduce ambiguity about epilepsy pathology, antiepileptic drugs, and effective therapeutic targets. Gut microbiota sequencing analysis reported that the level of Proteobacteria, Verrucomicrobia, Fusobacteria, and Firmicutes was increased and the level of Actinobacteria and Bacteroidetes was decreased in epilepsy patients. Clinical and preclinical studies also indicated that probiotics, ketogenic diet, faecal microbiota transplantation, and antibiotics can improve gut dysbiosis and alleviate seizure by enhancing the abundance of healthy biota. This study aims to give an overview of the connection between gut microbiota, and epilepsy, how gut microbiome changes may cause epilepsy, and whether gut microbiome restoration could be used as a treatment for epilepsy.

摘要

肠-脑轴增强了肠道与大脑之间的双向通信,并通过下丘脑-垂体-肾上腺轴、肠内分泌系统、神经内分泌系统、炎症和免疫途径调节肠道稳态和中枢神经系统。临床前和临床报告表明,肠道菌群失调可能在癫痫、帕金森病、多发性硬化症和阿尔茨海默病等神经系统疾病中起主要调节作用。癫痫是一种导致反复发作且无诱因癫痫发作的慢性神经系统疾病,癫痫的发生涉及众多风险因素。对肠道微生物群-脑轴的深入思考可以减少对癫痫病理学、抗癫痫药物和有效治疗靶点的模糊认识。肠道微生物群测序分析报告称,癫痫患者中变形菌门、疣微菌门、梭杆菌门和厚壁菌门的水平升高,而放线菌门和拟杆菌门的水平降低。临床和临床前研究还表明,益生菌、生酮饮食、粪便微生物群移植和抗生素可以通过增加健康生物群的丰度来改善肠道菌群失调并减轻癫痫发作。本研究旨在概述肠道微生物群与癫痫之间的联系、肠道微生物组变化如何导致癫痫,以及肠道微生物组恢复是否可作为癫痫的一种治疗方法。

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