The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity:Disruption of microbial composition and short-chain fatty acid metabolism  

作　　者：Lijian Chen Kaikai Zhang Jiali Liu Xiuwen Li Yi Liu Hongsheng M Jianzheng Yang Jiahao Li Long Chen Clare Hsu Jiahao Zeng Xiaoli Xie Qi Wang 

机构地区：[1]Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification,School of Forensic Medicine,Southern Medical University,Guangzhou 510515,China [2]Shunde Police in Foshan City,Foshan 528300,China [3]Department of Toxicology,School of Public Health,Southern Medical University(Guangdong Provincial Key Laboratory of Tropical Disease Research),Guangzhou 510515,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第11期4832-4857,共26页药学学报（英文版）

基　　金：National Natural Science Foundation of China(Grant Nos.82171877 and 82173474);Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2023A1515012476 and 2021A1515012456,China);Department of Science and Technology of Guangzhou city(Grant No.202002030043,China).

摘　　要：Methamphetamine(METH)abuse is associated with significant neurotoxicity,high addiction potential,and behavioral abnormalities.Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders.However,the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored.In this study,we employed fecal microbiota transplantation(FMT)and antibiotic(Abx)intervention to manipulate the gut microbiota in mice administered METH.Furthermore,we supplemented METH-treated mice with short-chain fatty acids(SCFAs)and pioglitazone(Pio)to determine the protective effects on gut microbiota metabolism.Finally,we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice.Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity,behavioral disorders,gut microbiota disturbances,and intestinal barrier impairment.Furthermore,our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH,which involves supplementation with SCFAs or Pio.

关 键 词：METHAMPHETAMINE Gut dysbiosis Behavioral disorders Wnt/β-Catenin/GSK3βsignaling pathway Fecal microbiota transplantation Short-chainfatty acid VAGOTOMY Microbiota-gut-brain axis 

分 类 号：R574[医药卫生—消化系统]