The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa
The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa
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DOI：
10.1038/s41598-019-40803-3
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发表时间：
2019-03-13
影响因子：
4.6
通讯作者：
Sprague, Jon E.
中科院分区：
文献类型：
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作者：
Ridge, Emily A.;Pachhain, Sudhan;Sprague, Jon E.
由3，4-亚甲二氧基甲基苯丙胺（MDMA）引起的体温过高可能危及生命。在这里，我们研究了肠道微生物组和TGR 5胆汁酸受体在MDMA介导的高热中的作用。在MDMA给药前14天，向雄性Sprague-Dawley大鼠提供水或经抗生素处理的水。接受抗生素的动物显示肠道细菌减少，对MDMA的高热反应减弱。MDMA处理的动物显示棕色脂肪组织和骨骼肌中解偶联蛋白1（UCP 1）和TGR 5表达水平增加，而仅在骨骼肌中观察到UCP 3表达增加。MDMA给药前的抗生素显著减弱了这些基因表达的增加。此外，用氨苯蝶啶抑制TGR 5受体或用碘番酸抑制TGR 5受体下游的脱碘酶II也导致MDMA诱导的体温过高的衰减。MDMA处理富集了未用抗生素预处理的动物盲肠中奇异变形杆菌菌株的相对比例。这些研究结果表明，肠道微生物群在MDMA介导的高热中起着重要作用，并且MDMA治疗可以引发肠道微生物群组成的快速重塑。
Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) can be life-threatening. Here, we investigate the role of the gut microbiome and TGR5 bile acid receptors in MDMA-mediated hyperthermia. Fourteen days prior to treatment with MDMA, male Sprague-Dawley rats were provided water or water treated with antibiotics. Animals that had received antibiotics displayed a reduction in gut bacteria and an attenuated hyperthermic response to MDMA. MDMA treated animals showed increased uncoupling protein 1 (UCP1) and TGR5 expression levels in brown adipose tissue and skeletal muscle while increased expression of UCP3 was observed only in skeletal muscle. Antibiotics prior to MDMA administration significantly blunted these increases in gene expression. Furthermore, inhibition of the TGR5 receptor with triamterene or of deiodinase II downstream of the TGR5 receptor with iopanoic acid also resulted in the attenuation of MDMA-induced hyperthermia. MDMA-treatment enriched the relative proportion of a Proteus mirabilis strain in the ceca of animals not pre-treated with antibiotics. These findings suggest a contributing role for the gut microbiota in MDMA-mediated hyperthermia and that MDMA treatment can trigger a rapid remodeling of the composition of the gut microbiome.