Zhang Jingyuan, Yang Jun, Yang Cheng, Chen Ti, Wang Ziwei, Li Junyi, Qin Fanglin, Deng Qijian, Zhang Xiaojie
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.
National Clinic Research Center for Mental Disorders, Changsha, China.
Front Psychiatry. 2020 Aug 28;11:631. doi: 10.3389/fpsyt.2020.00631. eCollection 2020.
Gut microbiota has been found to establish a bidirectional relationship with the central nervous system. Variations of the gut microbiota has been implicated in various mental disorders, including opioid use disorders. Morphine exposure has been repeatedly found to disrupt the gut microbiota, but association between the gut microbiota and the sensitivity to morphine reward remains unknown. In this study the conditioned place preference (CPP) paradigm was used for morphine-treated rats and saline-treated rats. After the CPP procedure, the morphine-treated rats were divided equally into the low and high CPP (L- and H-CPP) groups according to the CPP scores. We adopted 16S rRNA sequencing for the fecal bacterial communities at baseline and post-conditioning. By comparing the morphine-treated group with saline-treated group, we found alterations of microbial composition in the morphine-treated group, but no significant differences in alpha diversity. The L-CPP group and H-CPP group differed in microbial composition both before and after morphine treatment. The relative abundance of certain taxa was correlated to the CPP scores, such as and . This study provides direct evidence that morphine exposure alters the composition of the gut microbiota in rats and that microbial alterations are correlated to the sensitivity to morphine reward. These findings may help develop novel therapeutic and preventive strategies for opioid use disorder.
肠道微生物群已被发现与中枢神经系统建立了双向关系。肠道微生物群的变化与包括阿片类药物使用障碍在内的各种精神障碍有关。反复发现吗啡暴露会破坏肠道微生物群，但肠道微生物群与对吗啡奖赏的敏感性之间的关联仍然未知。在本研究中，条件性位置偏爱（CPP）范式用于吗啡处理的大鼠和生理盐水处理的大鼠。在CPP程序后，根据CPP评分将吗啡处理的大鼠平均分为低CPP和高CPP（L-CPP和H-CPP）组。我们对基线和条件反射后粪便细菌群落采用16S rRNA测序。通过比较吗啡处理组和生理盐水处理组，我们发现吗啡处理组的微生物组成发生了改变，但α多样性无显著差异。L-CPP组和H-CPP组在吗啡处理前后的微生物组成存在差异。某些分类群的相对丰度与CPP评分相关，如 和 。本研究提供了直接证据，表明吗啡暴露会改变大鼠肠道微生物群的组成，并且微生物改变与对吗啡奖赏的敏感性相关。这些发现可能有助于开发针对阿片类药物使用障碍的新型治疗和预防策略。
