Long-Term Effects of Developmental Exposure to Oxycodone on Gut Microbiota and Relationship to Adult Behaviors and Metabolism.
Long-Term Effects of Developmental Exposure to Oxycodone on Gut Microbiota and Relationship to Adult Behaviors and Metabolism.
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DOI：
10.1128/msystems.00336-22
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发表时间：
2022-08-30
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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阿片类药物是孕妇常用的镇痛药。直接暴露于这些药物可能会减缓肠道运动，改变肠道通透性，并影响肠道微生物群。虽然这些药物会影响婴儿的肠道微生物群，但迄今为止还没有研究确定发育过程中暴露于这些药物是否会对肠道微生物群产生长期影响，并相应地影响宿主的反应。我们假设发育过程中暴露于羟考酮（OXY）会导致肠道微生物群的持久影响，这种变化与成人神经行为和代谢变化有关。雌性小鼠在繁殖前2周和整个妊娠期间每天给予5mg /kg的氧或生理盐水（对照[CTL]）。雄性和雌性幼崽断奶，进行一系列行为和代谢测试，并在成年期（120日龄）收集粪便。在雌性中，与CTL个体相比，OXY个体中丁酸单胞菌、拟杆菌、无氧原体、TM7、肠球菌和梭状芽胞杆菌的相对丰度更高。在雄性中，暴露于氧的个体中，Coriobacteriaceae、Roseburia spp、Sutterella spp和Clostridia的相对丰度升高。细菌的变化也与代谢物途径的预测性改变有关，这种改变也因性别而异。在男性和女性中，受影响的肠道微生物群与代谢相关，但与行为改变无关。研究结果表明，发育过程中暴露于氧会对成人肠道微生物群产生持久影响，可能通过特定的细菌代谢物或其他细菌衍生产物影响宿主代谢。需要进一步的工作来描述发育暴露于氧如何通过肠道微生物组影响宿主反应。这是首次在啮齿动物模型中表明，在子宫内暴露于阿片类药物可导致成年后肠道微生物群的长期影响。此外，这种细菌变化与代谢宿主反应有关。考虑到啮齿类动物和人类微生物组之间的相似性，这引起了人们的担忧，即服用羟考酮和其他阿片类药物的母亲所生的孩子可能会出现明显的类似效果。
Opioid drugs are commonly prescribed analgesic to pregnant women. Direct exposure to such drugs may slow gut motility, alter gut permeability, and affect the gut microbiome. While such drugs affect gut microbiome in infants, no study to date has determined whether developmental exposure to such drugs results in longstanding effects on gut microbiota and correspondingly on host responses. We hypothesized developmental exposure to oxycodone (OXY) leads to enduring effects on gut microbiota and such changes are associated with adult neurobehavioral and metabolic changes. Female mice were treated daily with 5 mg OXY/kg or saline solution (control [CTL]) for 2 weeks prior to breeding and then throughout gestation. Male and female offspring pups were weaned, tested with a battery of behavioral and metabolic tests, and fecal boli were collected adulthood (120 days of age). In females, relative abundance of Butyricimonas spp., Bacteroidetes, Anaeroplasma spp., TM7, Enterococcus spp., and Clostridia were greater in OXY versus CTL individuals. In males, relative abundance of Coriobacteriaceae, Roseburia spp., Sutterella spp., and Clostridia were elevated in OXY exposed individuals. Bacterial changes were also associated with predictive metabolite pathway alterations that also varied according to sex. In males and females, affected gut microbiota correlated with metabolic but not behavioral alterations. The findings suggest that developmental exposure to OXY leads to lasting effects on adult gut microbiota that might affect host metabolism, possibly through specific bacterial metabolites or other bacterial-derived products. Further work is needed to characterize how developmental exposure to OXY affects host responses through the gut microbiome. IMPORTANCE This is the first work to show in a rodent model that in utero exposure to an opioid drug can lead to longstanding effects on the gut microbiota when examined at adulthood. Further, such bacterial changes are associated with metabolic host responses. Given the similarities between rodent and human microbiomes, it raises cause for concern that similar effects may become evident in children born to mothers taking oxycodone and other opioid drugs.
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影响因子：
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