Differential perturbations of gut microbial profiles and co-occurrence networks among phases of methamphetamine-induced conditioned place preference

The gut–brain axis provides a pathway for the interaction between gut microbiota and methamphetamine (METH) addiction. However, the gut microbial signatures during different phases of METH use remain unclear. In the present study, we established models of acquisition, extinction, and reinstatement of METH-induced conditioned place preference (CPP) in male mice and detected the gut microbiome profiles of the fecal samples at the three phases by 16S rRNA gene sequencing. Our results revealed that the richness of the gut microbiome increased following repeated METH administration, and it decreased after 4 weeks of abstinence. The microbial richness remained at a low level after one METH challenge at the reinstatement phase. The abundance of several genera including Prevotella, Bacteroides, and Lactobacillus differentially altered among phases of METH-induced CPP. The co-occurrence networks of the gut microbiome became weaker and more unstable during the development of METH-induced CPP at the extinction and reinstatement phases. Notably, the predicted gene functions of short-chain fatty acid metabolism, which were correlated with the abundance of Prevotella, Bacteroides, and Lactobacillus, were found differentially enriched among phases of METH-induced CPP. Our findings highlight a potential association between perturbations of the gut microbiome and different phases of METH use.