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

• DOI: 10.1016/j.biopha.2022.112837
• Publication Date: 2022-03-25T00:36:26Z
• Authors: Jiqing Yang; Zunyue Zhang; Zhenrong Xie; Ling Bai; Pu Xiong; Fengrong Chen; Tailin Zhu; Qingyan Peng; Hongjin Wu; Yong Zhou; Yuru Ma; Yongjin Zhang; Minghui Chen; Jianyuan Gao; Weiwei Tian; Kai Shi; Yan Du; Yong Duan; Huawei Wang; Yu Xu; Yi-Qun Kuang; Mei Zhu; Juehua Yu; Kunhua Wang
• Keywords: Methamphetamine; Meth-; Gut–brain axis

Metformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformin's participation the pathophysiology of withdrawal symptoms via modulation microbiota.In order to define functional impacts and metformin during METH withdrawal, we utilized a combination fecal transplantation (FMT), high-throughput sequencing, untargeted metabolomics technologies.First, addicts exhibited higher α diversity distinct microbial structures compared healthy controls. In particular, relative abundance Rikenellaceae was positively correlated with severity anxiety depression. Second, both human-to-mouse mouse-to-mouse FMTs confirmed that METH-altered-microbiota sufficient promote depression-like behaviours recipient germ-free mice, these disturbances could be ameliorated metformin. In-depth analysis revealed significantly altered bacterial composition structure as well several taxa metabolites, including inosine, respectively, whereas add-on remodel alterations. Finally, inosine complementation successfully restored METH-induced mice.This study demonstrates withdrawal-induced are reversible transmissible mouse model. The effects on manifestations associated microbiota-derived highlighting role substance use disorders symptoms.