Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS) function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP) were analyzed through 16S rRNA gene sequencing. The fecal microbial diversity was slightly higher in the METH CPP group. The propionate-producing genus Phascolarctobacterium was attenuated in the METH CPP group, and the family Ruminococcaceae was elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the fecal matter of METH-administered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.

Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS) function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamineinduced conditioned place preference (CPP) were analysed through 16S rRNA gene sequencing.The faecal microbial diversity was slightly higher in the METH CPP group. The propionateproducing genus Phascolarctobacterium was attenuated in the METH CPP group, and the family Ruminococcaceae was elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the faecal matter of METHadministered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.

BackgroundUnderstanding the process of relapse to abused drugs and ultimately developing treatments that can reduce the incidence of relapse remains the primary goal for the study of substance dependence. Therefore, exploring the metabolite characteristics during the relapse stage is valuable.MethodsA heroin self-administered rat model was employed, and analysis of the 1H-nuclear magnetic resonance-based metabolomics was performed to investigate the characteristic metabolite profile upon reintroduction to the drug after abstinence.ResultsSixteen metabolites in the serum of rats, including phospholipids, intermediates in TCA (Tricarboxylic Acid Cycle) cycle, keto bodies, and precursors for neurotransmitters, underwent a significant change in the reinstatement stage compared with those in the control group. In particular, energy production was greatly disturbed as evidenced by different aspects such as an increase in glucose and decrease in intermediates of glycolysis and the TCA cycle. The finding that the level of 3-hydroxybutyrate and acetoacetate increased significantly suggested that energy production was activated from fatty acids. The concentration of phenylalanine, glutamine, and choline, the precursors of major neurotransmitters, increased during the reinstatement stage which indicated that an alteration in neurotransmitters in the brain might occur along with the disturbance in substrate supply in the circulatory system.ConclusionsHeroin reinforcement resulted in impaired energy production via different pathways, including glycolysis, the TCA cycle, keto body metabolism, etc. A disturbance in the substrate supply in the circulatory system may partly explain heroin toxicity in the central nervous system. These findings provide new insight into the mechanism underlying the relapse to heroin use.Electronic supplementary materialThe online version of this article (10.1186/s12868-018-0404-5) contains supplementary material, which is available to authorized users.

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Background: The effect of contralateral prophylactic mastectomy (CPM) on the survival rate of triple-negative breast cancer (TNBC) patients is still controversial. The purpose of this study was to confirm whether unilateral TNBC patients benefit from CPM.Methods: 10006 patients with unilateral TNBC in the Surveillance, Epidemiology and End Results (SEER) database were enrolled in this study, propensity score matching (PSM) was applied to balance patient assignments. After PSM,3039 pairs of patients were divided into a CPM group and no-CPM group, respectively. All the patients have undergone total mastectomy or radical mastectomy. Cox proportional hazards regression models were used to evaluate overall survival (OS) and breast cancer-specific survival (BCSS) of the two groups. Subgroup analysis was introduced to exclude the effect of confounding factors. To identify potential variables for prognosis, Kaplan–Meier survival analysis and Cox regression analysis were used and were presented by Kaplan–Meier curve and forest plot separately.Results: With a median follow‐up time of 34.5months (IQR 1–83 months), the estimated 5-year BCSS rates for patients in the CPM group and the no-CPM group were 81.96% and 78.71%, the 5-year OS rates were 80.10% and 75.05%, respectively. CPM improved the BCSS (hazard ratio [HR]= 0.79; 95% confidence interval [CI]=0.69-0.90, p=0.001) and OS (HR= 0.74; 95% CI=0.66-0.84, p<0.001) of unilateral TNBC patients. Univariate subgroup analyses revealed that there was no significant difference in survival time for patients in stage N3 who underwent CPM or not (p>0.05).Conclusions: CPM only limitedly improved BCSS and OS in patients with unilateral TNBC undergoing total mastectomy or radical mastectomy and was not recommended for stage N3 patients.