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.

中文翻译：

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甲基苯丙胺诱导的条件性位置偏好各阶段肠道微生物谱和共现网络的差异扰动

肠-脑轴为肠道微生物群与甲基苯丙胺 (METH) 成瘾之间的相互作用提供了途径。然而，METH 使用不同阶段的肠道微生物特征仍不清楚。在本研究中，我们建立了 METH 诱导的雄性小鼠条件性位置偏好 (CPP) 的获得、灭绝和恢复模型，并通过 16S rRNA 基因测序检测了三个阶段粪便样本的肠道微生物组谱。我们的研究结果表明，重复服用 METH 后肠道微生物组的丰富度增加，禁欲 4 周后减少。在恢复阶段进行一次 METH 挑战后，微生物丰富度保持在较低水平。包括普氏菌属、拟杆菌属在内的几个属的丰度，和乳酸杆菌在 METH 诱导的 CPP 阶段之间发生差异变化。在 METH 诱导的 CPP 在灭绝和恢复阶段的发展过程中，肠道微生物组的共现网络变得更弱和更不稳定。值得注意的是，预测的短链脂肪酸代谢基因功能与普氏菌属、拟杆菌属和乳杆菌属的丰度相关，在 METH 诱导的 CPP 的各个阶段之间存在差异富集。我们的研究结果强调了肠道微生物组的扰动与 METH 使用的不同阶段之间的潜在关联。