Alterations in the oral microbiome and metabolome of methamphetamine addicts. Alterations in the oral microbiome and metabolome of methamphetamine addicts

Drug addiction can seriously damage human physical and mental health, and detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) addicts, the role of the microbiome in this process still needs further study. This study aims to explore the function of the microbiome by jointly analyzing the changes in the oral microbiome and metabolome of METH addicts.We performed 16S rRNA sequencing on oral saliva samples collected from 278 METH addicts and 105 healthy controls (CTL) undergoing detoxification at detoxification centers in Shandong, China. In addition, untargeted metabolomic profiling was conducted on 220 samples (170 METH addicts and 50 CTL) to identify biomarkers and build classifiers for both oral microbiota and metabolites.Compared to the CTL group, alpha diversity is reduced in the METH addicts group, with significant differences in the microbiota, which are accompanied by changes in oral metabolic pathways. These pathways include enhanced tryptophan metabolism, biosynthesis of lysine, purine metabolism, and steroid biosynthesis. Conversely, metabolic pathways such as porphyrin metabolism, glutathione metabolism, and pentose phosphate pathway are significantly reduced. We speculate that four key microbiota, Peptostreptococcus, Gemella, Campylobacter and Aggregatibacter may be involved in the toxicity and addiction mechanisms of METH by affecting these metabolic pathways. In addition, microbial prediction models are more effective than metabolite-based prediction models in identifying METH addiction.Our data has identified potential functional links between the oral microbiome and metabolic profile of METH addicts, providing new insights into exploring the toxic damage and addiction mechanisms related to METH.