Department of Veterinary Population Medicine, University of Minnesota, 225 VMC 1365 Gortner Ave., St Paul, MN, 55108, USA.
Department of Surgery and Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida, 33101, USA.
Sci Rep. 2018 Feb 26;8(1):3596. doi: 10.1038/s41598-018-21915-8.
Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious comorbidities, such as dependence, tolerance, immunosuppression and gastrointestinal disorders limit their long-term use. In the current study, a morphine-murine model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the negative consequences associated with opioid use. Results reveal a significant shift in the gut microbiome and metabolome within one day following morphine treatment compared to that observed after placebo. Morphine-induced gut microbial dysbiosis exhibited distinct characteristic signatures, including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance and significant impairment in bile acids and morphine-3-glucuronide/morphine biotransformation in the gut. Moreover, expansion of Enterococcus faecalis was strongly correlated with gut dysbiosis following morphine treatment, and alterations in deoxycholic acid (DCA) and phosphatidylethanolamines (PEs) were associated with opioid-induced metabolomic changes. Collectively, these results indicate that morphine induced distinct alterations in the gut microbiome and metabolome, contributing to negative consequences associated with opioid use. Therapeutics directed at maintaining microbiome homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
阿片类镇痛药在美国和全球范围内经常被开处方。然而，严重的合并症，如依赖、耐受、免疫抑制和胃肠道疾病，限制了它们的长期使用。在目前的研究中，使用吗啡-小鼠模型来研究肠道微生物组和代谢组作为导致与阿片类药物使用相关的负面后果的潜在机制的作用。结果显示，与安慰剂相比，吗啡治疗后一天内肠道微生物组和代谢组发生显著变化。吗啡诱导的肠道微生物失调表现出独特的特征签名，包括与致病性功能相关的群落显著增加，与应激耐受相关的群落减少，以及肠道胆汁酸和吗啡-3-葡萄糖醛酸/吗啡生物转化的显著损害。此外，粪肠球菌的扩张与吗啡治疗后肠道失调密切相关，脱氧胆酸（DCA）和磷脂酰乙醇胺（PE）的改变与阿片类药物引起的代谢组变化有关。总的来说，这些结果表明，吗啡诱导了肠道微生物组和代谢组的明显改变，导致了与阿片类药物使用相关的负面后果。在阿片类药物使用期间靶向维持微生物组平衡的治疗方法可能会减少与阿片类药物用于疼痛管理相关的合并症。
