Metformin acts on the gut-brain axis to ameliorate antipsychotic-induced metabolic dysfunction

Xiaorong Wang; Huimin Huang; Yiyi Zhu; Shaoli Li; Peifen Zhang; Jiajun Jiang; Caixi Xi; Lingling Wu; Xingle Gao; Yaoyang Fu; Danhua Zhang; Yiqing Chen; Shaohua Hu; Jianbo Lai

doi:10.5582/bst.2021.01317

Review

Metformin acts on the gut-brain axis to ameliorate antipsychotic-induced metabolic dysfunction

Xiaorong Wang, Huimin Huang, Yiyi Zhu, Shaoli Li, Peifen Zhang, Jiajun Jiang, Caixi Xi, Lingling Wu, Xingle Gao, Yaoyang Fu, Danhua Zhang, Yiqing Chen, Shaohua Hu, Jianbo Lai

Author information

Xiaorong Wang
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, Zhejiang, China.
Brain Research Institute of Zhejiang University, Hangzhou, Zhejiang, China.
Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, Zhejiang, China.
Huimin Huang
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yiyi Zhu
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Wenzhou Medical University, Wenzhou, Zhejiang, China.
Shaoli Li
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Peifen Zhang
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Jiajun Jiang
The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, Zhejiang, China.
Caixi Xi
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Lingling Wu
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Xingle Gao
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Yaoyang Fu
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Danhua Zhang
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Yiqing Chen
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Shaohua Hu
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, Zhejiang, China.
Brain Research Institute of Zhejiang University, Hangzhou, Zhejiang, China.
Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, Zhejiang, China.
Jianbo Lai
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, Zhejiang, China.
Brain Research Institute of Zhejiang University, Hangzhou, Zhejiang, China.
Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, Zhejiang, China.

Keywords: antipsychotic-induced metabolic dysfunction, gut-brain axis, gut microbiota, metformin, hypothalamus, neuropeptide

JOURNAL FREE ACCESS

2021 Volume 15 Issue 5 Pages 321-329

DOI https://doi.org/10.5582/bst.2021.01317

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Abstract

Antipsychotic-induced metabolic dysfunction (AIMD) is an intractable clinical challenge worldwide. The situation is becoming more critical as second-generation antipsychotics (SGAs), to a great extent, have replaced the role of first-generation antipsychotics in managing major psychiatric disorders. Although the exact mechanisms for developing AIMD is intricate, emerging evidence has indicated the involvement of the microbiota-gut-brain axis in AIMD. SGAs treatment may change the diversity and compositions of intestinal flora (e.g., decreased abundance of Bacteroidetes and Akkermansia muciniphila, and increased Firmicutes). Short-chain fatty acids and other metabolites derived from gut microbiota, on the one hand, can regulate the activity of intestinal endocrine cells and their secretion of satiety hormones (e.g., glucagon-like peptide 1, peptide YY, cholecystokinin and ghrelin); on the other hand, can activate the vagus nerve or transport into the brain to exert a central modulation of foraging behaviors via binding to neuropeptide receptors. Interestingly, metformin, a classical antidiabetic agent, is capable of alleviating AIMD possibly by regulating the microbiota-gut-brain axis. That is, metformin can not only partially reverse the alterations of gut microbial communities due to SGAs treatment, but also play a positive role in rectifying the disturbances of peripheral and central satiety-related neuropeptides. Current evidence has indicated a promising role for metformin on ameliorating AMID, but further verifications in well-designed clinical trials are still warranted.

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