BioScience Trends. 2021;15(5):321-329. (DOI: 10.5582/bst.2021.01317)

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

Wang XR, Huang HM, Zhu YY, Li SL, Zhang PF, Jiang JJ, Xi CX, Wu LL, Gao XL, Fu YY, Zhang DH, Chen YQ, Hu SH, Lai JB


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 microbiotagut- 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.

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

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