Fecal microbial transplantation (FMT) affects methylone induced tolerance in rats

The role of the microbiome-gut-brain axis in modulating body temperatures has been well document over the past few years. However, its role of regulating body temperatures in response to drug induction remains unexplored. Here we assessed the functions of gut microbiota in moderating thermogenic responses to the drug methylone, a potent psychostimulant. For this study, male Sprague Dawley rats were either untreated or treated with a non-lethal dose of methylone for a period of 4 weeks. Following the development of tolerance in methylone treated rats, animals were subjected to fecal microbial transplantation. Daily fecal droppings were collected and cross-fed across animals of both groups. We traced changes in the gut microbiome performed via 16S amplicon sequencing (V3-V4 region). The analysis revealed alterations of relative abundances of species belonging to the classes Gammaproteobacteria, Alphaproteobacteria and Erysipelotrichia post-FMT. This data indicated the potential role of these classes in modulating methylone induced thermogenic responses. We measured changes in body temperatures, plasma norepinephrine levels and expression levels of genes coordinating thermogenesis throughout the course of the study.

过去数年中，微生物群-肠-脑轴（microbiome-gut-brain axis）对体温的调控作用已得到充分证实。然而，其在药物诱导情境下的体温调控作用仍未被探索。本研究评估了肠道菌群对强效精神兴奋剂亚甲二氧甲基苯丙胺（methylone）诱导的产热反应的调控作用。本研究中，将雄性斯普拉格-道利大鼠（Sprague Dawley rats）分为两组：一组不予任何处理，另一组给予非致死剂量的亚甲二氧甲基苯丙胺，连续给药4周。待亚甲二氧甲基苯丙胺给药组大鼠产生耐受性后，对所有大鼠实施粪便微生物移植（fecal microbial transplantation, FMT）。每日收集粪便样本，并在两组大鼠间开展交叉粪便移植操作。通过16S扩增子测序（16S amplicon sequencing，V3-V4区）追踪肠道菌群的变化。分析结果显示，粪便微生物移植后，γ-变形菌纲（Gammaproteobacteria）、α-变形菌纲（Alphaproteobacteria）以及丹毒丝菌纲（Erysipelotrichia）内物种的相对丰度发生了显著改变。上述数据表明，这些细菌纲在调控亚甲二氧甲基苯丙胺诱导的产热反应中存在潜在作用。本研究全程监测了大鼠体温、血浆去甲肾上腺素水平以及产热相关基因的表达变化。