Wynendaele Evelien, Verbeke Frederick, Stalmans Sofie, Gevaert Bert, Janssens Yorick, Van De Wiele Christophe, Peremans Kathelijne, Burvenich Christian, De Spiegeleer Bart
Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Department of Radiology and Nuclear Medicine, Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent, Belgium.
PLoS One. 2015 Nov 4;10(11):e0142071. doi: 10.1371/journal.pone.0142071. eCollection 2015.
Bacteria communicate with each other by the use of signaling molecules, a process called 'quorum sensing'. One group of quorum sensing molecules includes the oligopeptides, which are mainly produced by Gram-positive bacteria. Recently, these quorum sensing peptides were found to biologically influence mammalian cells, promoting i.a. metastasis of cancer cells. Moreover, it was found that bacteria can influence different central nervous system related disorders as well, e.g. anxiety, depression and autism. Research currently focuses on the role of bacterial metabolites in this bacteria-brain interaction, with the role of the quorum sensing peptides not yet known. Here, three chemically diverse quorum sensing peptides were investigated for their brain influx (multiple time regression technique) and efflux properties in an in vivo mouse model (ICR-CD-1) to determine blood-brain transfer properties: PhrCACET1 demonstrated comparatively a very high initial influx into the mouse brain (Kin = 20.87 μl/(g×min)), while brain penetrabilities of BIP-2 and PhrANTH2 were found to be low (Kin = 2.68 μl/(g×min)) and very low (Kin = 0.18 μl/(g×min)), respectively. All three quorum sensing peptides were metabolically stable in plasma (in vitro) during the experimental time frame and no significant brain efflux was observed. Initial tissue distribution data showed remarkably high liver accumulation of BIP-2 as well. Our results thus support the potential role of some quorum sensing peptides in different neurological disorders, thereby enlarging our knowledge about the microbiome-brain axis.
细菌通过使用信号分子相互交流，这一过程称为“群体感应”。一类群体感应分子包括寡肽，主要由革兰氏阳性菌产生。最近，人们发现这些群体感应肽对哺乳动物细胞具有生物学影响，尤其会促进癌细胞转移。此外，还发现细菌会影响不同的中枢神经系统相关疾病，如焦虑症、抑郁症和自闭症。目前的研究重点是细菌代谢产物在这种细菌与大脑相互作用中的作用，而群体感应肽的作用尚不清楚。在此，研究了三种化学性质不同的群体感应肽在体内小鼠模型（ICR-CD-1）中的脑内流入（多次回归技术）和流出特性，以确定血脑转移特性：PhrCACET1在小鼠脑中表现出相对较高的初始流入量（Kin = 20.87 μl/(g×min)），而BIP-2和PhrANTH2的脑穿透性较低（Kin = 2.68 μl/(g×min)）和非常低（Kin = 0.18 μl/(g×min)）。在实验时间范围内，所有三种群体感应肽在血浆中（体外）代谢稳定，未观察到明显的脑流出。初始组织分布数据还显示BIP-2在肝脏中的积累也非常高。因此，我们的结果支持了一些群体感应肽在不同神经疾病中的潜在作用，从而扩展了我们对微生物组-脑轴的认识。
