Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses.
Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses.
复制标题
DOI：
10.1016/j.chom.2022.09.014
复制
发表时间：
2022-11-09
影响因子：
30.3
通讯作者：
Sperandio, Vanessa
中科院分区：
文献类型：
--
作者：
Cuesta, Santiago;Burdisso, Paula;Segev, Amir;Kourrich, Said;Sperandio, Vanessa
肠道微生物群成员与不同的神经心理学结果相关，包括物质使用障碍（SUD）。在这里，我们使用小鼠与柠檬酸杆菌啮齿类或人类γ-变形杆菌大肠杆菌HS作为模型，以检查肠道微生物和宿主对可卡因的反应之间的机制相互作用。我们发现可卡因暴露增加肠道去甲肾上腺素水平，其通过细菌肾上腺素能受体QseC感知以促进γ-变形菌的肠道定殖。定殖小鼠表现出增强的宿主可卡因诱导的行为。神经活性代谢物甘氨酸是细菌氮源，在定植小鼠的肠道和脑脊液中耗尽。系统性甘氨酸补充逆转，并且甘氨酸摄取突变的γ-变形菌没有改变宿主对可卡因的反应。γ-变形菌调节甘氨酸水平与可卡因诱导的转录可塑性有关。这里概述的机制可能被用来调节与奖励相关的大脑回路，从而导致SUD。Cuesta等人在小鼠中证明，可卡因暴露增加肠道中的去甲肾上腺素，促进变形菌定植。这种肠道微生物群向变形菌的转变导致宿主中甘氨酸的耗尽，这反过来又促进了小鼠中可卡因诱导的成瘾样行为。
Gut-microbiota membership is associated with diverse neuropsychological outcomes, including substance use disorders (SUDs). Here, we use mice colonized with Citrobacter rodentium or the human γ-Proteobacteria commensal Escherichia coli HS as a model to examine the mechanistic interactions between gut microbes and host responses to cocaine. We find that cocaine exposure increases intestinal norepinephrine levels that is sensed through the bacterial adrenergic receptor QseC to promote intestinal colonization of γ-Proteobacteria. Colonized mice showed enhanced host cocaine-induced behaviors. The neuroactive metabolite glycine, a bacterial nitrogen source is depleted in the gut and cerebrospinal fluid of colonized mice. Systemic glycine repletion reversed, and γ-Proteobacteria mutated for glycine uptake did not alter the host response to cocaine. γ-Proteobacteria modulated glycine levels are linked to cocaine-induced transcriptional plasticity in the nucleus accumbens through glutamatergic transmission. The mechanism outline here could potentially be exploited to modulate reward-related brain circuits that contribute to SUDs. Cuesta et al. demonstrate in mice that cocaine exposure increases norepinephrine in the gut facilitating Proteobacteria colonization. This gut microbiota shift toward proteobacteria leads to a depletion of glycine from the host, which, in turn, facilitates cocaine-induced addiction-like behaviors in mice.
登录
查看更多内容
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
4.7
作者：
Carmen Blanco-Gandia, M.;Cantacorps, Lidia;Rodriguez-Arias, Marta
通讯作者：
Rodriguez-Arias, Marta
影响因子：
14.5
作者：
Curcio, Livia;Podda, Maria V.;D'Ascenzo, Marcello
通讯作者：
D'Ascenzo, Marcello
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
3.4
作者：
Baladi, Michelle G.;Koek, Wouter;France, Charles P.
通讯作者：
France, Charles P.