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

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...

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Published in:Acta pharmaceutica Sinica. B 2024-11, Vol.14 (11), p.4832-4857
Main Authors: Chen, Lijian, Zhang, Kaikai, Liu, Jiali, Li, Xiuwen, Liu, Yi, Ma, Hongsheng, Yang, Jianzheng, Li, Jiahao, Chen, Long, Hsu, Clare, Zeng, Jiahao, Xie, Xiaoli, Wang, Qi
Format: Article
Language:English
Subjects:
Behavioral disorders
Fecal microbiota transplantation
Gut dysbiosis
Methamphetamine
Microbiota–gut–brain axis
Original
Short-chain fatty acid
Vagotomy
Wnt/β-Catenin/GSK3β signaling pathway
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Summary: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. Gut microbiota involved in METH-induced neurotoxicity. SCFAs and Pio ameliorated METH-induced neurotoxicity, depending on vagus nerve integrity. [Display omitted]
ISSN:2211-3835
2211-3843
DOI:10.1016/j.apsb.2024.08.012