Study M917

Study name

Yang JQ 2022

Title

Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice

Overall design

The aim of this study was to explore the effects of metformin on gut microbiota, microbial metabolism, and neurobehavioral symptoms induced by methamphetamine exposure. The authors showed that both human-to-mouse and mouse-to-mouse fecal microbiota transplantation (FMT) confirmed that methamphetamine-altered microbiota transplantation is sufficient to promote depression and anxiety-like behaviors, and these behavioral disturbances could be ameliorated by metformin. Then C57BL/6 mice were divided into the following 3 groups: (1) FMT saline group (antibiotics-treated mice received FMT from mice treated with saline), (2) FMT methamphetamine group (antibiotics-treated mice received FMT from mice treated with methamphetamine), and (3) FMT methamphetamine + metformin group (antibiotics-treated mice received FMT from mice treated with both methamphetamine and metformin). The results of behavioral tests showed that mice receiving FMT from methamphetamine-treatment mice showed depression-like behaviors compared with mice receiving FMT from saline-treatment mice; while mice transplanted with metformin-treated fecal microbiota showed lower anxiety-like and depression-related behaviors. Metabolomic analyzes of fecal samples were performed (n = 8-9/ per group).

Study Type

Type1;

Type2;

Data available

Unavailable

Organism

Mouse; C57BL/6 mouse;

Categories of depression

Animal model; Other animal model; Other animal model;

Criteria for depression

Forced swimming test, tail suspension test

Sample size

25

Tissue

Peripheral; Faece; Faece;

Platform

MS-based; LC-MS: ultra-high-performance liquid chromatography (UHPLC, 1290 Infinity LC, Agilent Technologies, Santa Clara, CA, USA) with quadrupole time of-flight system (AB Sciex Triple TOF 6600, AB SCIEX);

PMID

35339829

DOI

10.1016/j.biopha.2022.112837

Citation

Yang J, Zhang Z, Xie Z, et al. Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice. Biomed Pharmacother. 2022 May;149:112837.

Metabolite

Inosine;

Allantoin;

Ketoleucine;

Folinic acid;