Microbial glutamate metabolism predicts intravenous cocaine self-administration in diversity outbred mice.
Microbial glutamate metabolism predicts intravenous cocaine self-administration in diversity outbred mice.
复制标题
微生物谷氨酸代谢预测多样性远交小鼠静脉注射可卡因的自我给药。
DOI：
10.1016/j.neuropharm.2022.109409
复制
发表时间：
2023-03-15
影响因子：
4.7
通讯作者：
Bubier, Jason A.
中科院分区：
文献类型：
--
作者：
Tran, Thi Dong Binh;Nguyen, Hoan;Sodergren, Erica;Dickson, Price E.;Wright, Susan N.;Philip, Vivek M.;Weinstock, George M.;Chesler, Elissa J.;Zhou, Yanjiao;Bubier, Jason A.
肠道微生物组被认为在精神疾病的发生和发展中起着关键作用，包括抑郁症和物质使用障碍（SUD）。为了验证微生物组影响成瘾倾向行为和可卡因静脉自我给药（IVSA）的假设，并确定参与这种关系的特定微生物，我们对228只不同远交小鼠的粪便进行了16 S rRNA基因测序。获得可卡因IVSA（ACQ）的小鼠和未能获得IVSA（FACQ）的小鼠之间的12个开放领域的措施，两个光暗测定措施，一个孔板和新奇的位置偏好措施显着不同。我们发现，ACQ小鼠比FACQ小鼠更活跃，更具探索性，表现出更少的恐惧。ACQ小鼠中的Barnesiella、Ruminococcus和Robinsoniella丰度增加，Clostridium IV丰度减少，这是ACQ小鼠与FACQ小鼠的区别。ACQ和微生物丰度之间存在性别特异性相关性，ACQ雄性小鼠中乳酸菌丰度降低，ACQ雌性小鼠中布劳特氏菌丰度降低。Robinsoniella的丰度是相关的，梭状芽孢杆菌IV与在收购过程中自我管理的可卡因剂量的数量呈负相关。对小鼠亚组的微生物组组成的功能分析表明，编码谷氨酸代谢基因的肠-脑模块与自我施用可卡因的倾向有关。这些发现建立了微生物组组成和谷氨酸代谢潜力与获得可卡因IVSA的能力之间的关联，从而表明靶向肠道微生物组或微生物代谢物治疗SUD的潜在转化影响。本文是“微生物组与大脑：机制与疾病”特刊的一部分。
The gut microbiome is thought to play a critical role in the onset and development of psychiatric disorders, including depression and substance use disorder (SUD). To test the hypothesis that the microbiome affects addiction predisposing behaviors and cocaine intravenous self-administration (IVSA) and to identify specific microbes involved in the relationship, we performed 16S rRNA gene sequencing on feces from 228 diversity outbred mice. Twelve open field measures, two light-dark assay measures, one hole board and novelty place preference measure significantly differed between mice that acquired cocaine IVSA (ACQ) and those that failed to acquire IVSA (FACQ). We found that ACQ mice are more active and exploratory and display decreased fear than FACQ mice. The microbial abundances that differentiated ACQ from FACQ mice were an increased abundance of Barnesiella, Ruminococcus, and Robinsoniella and decreased Clostridium IV in ACQ mice. There was a sex-specific correlation between ACQ and microbial abundance, a reduced Lactobacillus abundance in ACQ male mice, and a decreased Blautia abundance in female ACQ mice. The abundance of Robinsoniella was correlated, and Clostridium IV inversely correlated with the number of doses of cocaine self-administered during acquisition. Functional analysis of the microbiome composition of a subset of mice suggested that gut-brain modules encoding glutamate metabolism genes are associated with the propensity to self-administer cocaine. These findings establish associations between the microbiome composition and glutamate metabolic potential and the ability to acquire cocaine IVSA thus indicating the potential translational impact of targeting the gut microbiome or microbial metabolites for treatment of SUD. This article is part of the Special Issue on “Microbiome & the Brain: Mechanisms & Maladies”.
登录
查看更多内容
DOI：
10.1007/s00335-021-09884-2
发表时间：
2021-08
期刊：
Mammalian genome : official journal of the International Mammalian Genome Society
影响因子：
--
作者：
Bubier JA;Chesler EJ;Weinstock GM
通讯作者：
Weinstock GM
影响因子：
4.6
作者：
Chivero, Ernest T.;Ahmad, Rizwan;Buch, Shilpa
通讯作者：
Buch, Shilpa
影响因子：
4.7
作者：
Chun, Kyung-Soo;Lao, Huei-Chen;Langenbach, Robert
通讯作者：
Langenbach, Robert
影响因子：
3.4
作者：
Dickson, Price E.;Ndukum, Juliet;Chesler, Elissa J.
通讯作者：
Chesler, Elissa J.
肠道菌群对小鼠海马 microRNA 和 mRNA 表达的影响
影响因子：
2.7
作者：
Chen, Jian-jun;Zeng, Ben-hua;Xie, Peng
通讯作者：
Xie, Peng