The gut microbiome contributes to somatic morphine withdrawal behavior and implicates a TLR2 mediated mechanism.
The gut microbiome contributes to somatic morphine withdrawal behavior and implicates a TLR2 mediated mechanism.
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DOI：
10.1080/19490976.2023.2242610
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发表时间：
2023-01
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
作者：
由于高度成瘾性物质的过度处方，持续的阿片类流行病使数百万人患有阿片类药物使用障碍。慢性阿片类药物暴露导致依赖，缺乏药物导致阴性戒断症状，往往促使患者继续使用药物；然而，目前很少有治疗策略可用于对抗成瘾循环和吗啡戒断的严重程度。本研究探讨了微生物组作为吗啡戒断的潜在治疗靶点，因为吗啡使用引起的肠道生态失调已被证明有助于阿片类药物使用障碍的其他方面，如耐受性。结果表明，尽管吗啡戒断期间的微生物群有从吗啡诱导的生态失调中恢复的趋势，但α和β的多样性以及革兰氏阳性细菌的丰度仍然存在破坏，这可能仍然导致吗啡戒断症状的严重程度。缺乏微生物组的无菌小鼠没有出现躯体戒断症状，表明微生物组对于躯体戒断行为的发展是必要的。值得注意的是，只有TLR2而不是TLR4全身敲除模型显示出较低的戒断严重程度，这意味着微生物组通过革兰氏阳性TLR2介导的机制驱动阿片类药物诱导的躯体戒断行为。
The ongoing opioid epidemic has left millions of people suffering from opioid use disorder due to the over-prescription of highly addictive substances. Chronic opioid exposure leads to dependence, where the absence of the drug results in negative symptoms of withdrawal, often driving patients to continue drug use; however, few therapeutic strategies are currently available to combat the cycle of addiction and the severity of morphine withdrawal. This study investigates the microbiome as a potential therapeutic target for morphine withdrawal, as gut dysbiosis caused by morphine use has been proven to contribute to other aspects of opioid use disorders, such as tolerance. Results show that although the microbiome during morphine withdrawal trends toward recovery from morphine-induced dysbiosis, there continues to be a disruption in the alpha and beta diversity as well as the abundance of gram-positive bacteria that may still contribute to the severity of morphine withdrawal symptoms. Germ-free mice lacking the microbiome did not develop somatic withdrawal symptoms, indicating that the microbiome is necessary for the development of somatic withdrawal behavior. Notably, only TLR2 but not TLR4 whole-body knockout models display less withdrawal severity, implicating that the microbiome, through a gram-positive, TLR2 mediated mechanism, drives opioid-induced somatic withdrawal behavior.
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影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
2.5
作者：
Bobzean, Samara A. M.;Kokane, Saurabh S.;Perrotti, Linda I.
通讯作者：
Perrotti, Linda I.
影响因子：
1.6
作者：
Brewer, Abigail L.;Lewis, Christina C.;Quock, Raymond M.
通讯作者：
Quock, Raymond M.
DOI：
10.1093/jurban/79.2.266
发表时间：
2002-06-01
影响因子：
6.6
作者：
Sherman, SG;Latkin, CA
通讯作者：
Latkin, CA
影响因子：
3.5
作者：
Park AJ;Collins J;Blennerhassett PA;Ghia JE;Verdu EF;Bercik P;Collins SM
通讯作者：
Collins SM