Fecal microbiota transplantation and antibiotic treatment attenuate naloxone-precipitated opioid withdrawal in morphine-dependent mice.
Fecal microbiota transplantation and antibiotic treatment attenuate naloxone-precipitated opioid withdrawal in morphine-dependent mice.
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粪便微生物群移植和抗生素治疗可减轻吗啡依赖小鼠中纳洛酮诱发的阿片类药物戒断反应。
DOI：
10.1016/j.expneurol.2021.113787
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发表时间：
2021-09
影响因子：
5.3
通讯作者：
Hohmann AG
中科院分区：
文献类型：
--
作者：
Thomaz AC;Iyer V;Woodward TJ;Hohmann AG
阿片成瘾会产生严重的副作用，包括身体依赖和戒断。最近，肠道微生物群的扰动被证明可以改变阿片类药物诱导的副作用，如成瘾、耐受和依赖。在本研究中，我们通过评估粪便微生物区系移植(FMT)、抗生素和益生菌治疗以及药物抑制阿片类药物依赖小鼠肠道通透性的效果，来研究肠道微生物群对阿片类药物戒断的影响。重复腹腔注射(I.P.)吗啡治疗产生的身体依赖是通过测量使用阿片类拮抗剂纳洛酮引起的躯体戒断迹象(即跳跃次数)来量化的。与接受生理盐水处理的供体小鼠的FMT的吗啡依赖小鼠相比，接受来自吗啡治疗的供体小鼠的FMT的吗啡依赖小鼠表现出较少的纳洛酮沉淀跳跃。小鼠盲肠中的微生物含量因吗啡处理而改变，但不受FMT的影响。一种广谱抗生素鸡尾酒疗法减少了吗啡依赖小鼠的细菌负荷，并减轻了纳洛酮催促的吗啡戒断，而商业上可获得的益生菌菌株并不可靠地改变阿片类药物戒断的体征。肠道通透性的药理抑制剂ML-7可降低吗啡引起的体内肠道通透性增加，但不能可靠地改变纳洛酮催促的阿片类药物戒断的躯体体征。我们的结果表明，肠道微生物群影响慢性吗啡诱导的身体依赖的发展，肠道微生物群的治疗性操作可能会减少阿片类药物的戒断。
Opioid addiction can produce severe side effects including physical dependence and withdrawal. Perturbations of the gut microbiome have recently been shown to alter opioid-induced side-effects such as addiction, tolerance and dependence. In the present study, we investigated the influence of the gut microbiome on opioid withdrawal by evaluating the effects of fecal microbiota transplantation (FMT), antibiotic and probiotic treatments, and pharmacological inhibition of gut permeability in a mouse model of opioid dependence. Repeated intraperitoneal (i.p.) morphine treatment produced physical dependence that was quantified by measuring somatic signs of withdrawal (i.e. number of jumps) precipitated using the opioid antagonist naloxone. Morphine-dependent mice that received FMT from morphine-treated donor mice exhibited fewer naloxone-precipitated jumps compared to morphine-dependent counterparts receiving FMT from saline-treated donor mice. Microbial contents in the mouse cecum were altered by morphine treatment but were not differentially impacted by FMT. A broad-spectrum antibiotic cocktail regimen reduced the bacterial load and attenuated naloxone-precipitated morphine withdrawal in morphine-dependent mice, whereas commercially available probiotic strains did not reliably alter somatic signs of opioid withdrawal. ML-7, a pharmacological inhibitor of gut permeability, reduced the morphine-induced increase in gut permeability in vivo but did not reliably alter somatic signs of naloxone-precipitated opioid withdrawal. Our results suggest that the gut microbiome impacts the development of physical dependence induced by chronic morphine administration, and that therapeutic manipulations of the gut microbiome may reduce opioid withdrawal.
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影响因子：
9.8
作者：
Bojanova DP;Bordenstein SR
通讯作者：
Bordenstein SR
影响因子：
4.8
作者：
Huppert, Jula;Closhen, Dorothea;Kuhlmann, Christoph R. W.
通讯作者：
Kuhlmann, Christoph R. W.
影响因子：
3.7
作者：
Gu S;Chen D;Zhang JN;Lv X;Wang K;Duan LP;Nie Y;Wu XL
通讯作者：
Wu XL
影响因子：
3.7
作者：
Barengolts E;Green SJ;Eisenberg Y;Akbar A;Reddivari B;Layden BT;Dugas L;Chlipala G
通讯作者：
Chlipala G
DOI：
10.1152/ajpgi.00142.2012
发表时间：
2013-01-01
影响因子：
4.5
作者：
Ganguli, Kriston;Meng, Di;Nanthakumar, Nanda
通讯作者：
Nanthakumar, Nanda