Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Department of Physiology, Southwest Medical University, Luzhou, China.
Ann N Y Acad Sci. 2020 Jun;1470(1):14-24. doi: 10.1111/nyas.14312. Epub 2020 Feb 28.
The blood-brain barrier (BBB) contributes to the maintenance of brain homeostasis. Gut microbiome composition affects BBB development and expression of tight junction proteins in rodents. However, we still do not know if there is any direct effect of gut microbial composition on BBB permeability and function in normal adult animals. In the current study, we determined temporal and spatial changes in BBB permeability of rhesus monkeys receiving amoxicillin-clavulanic acid (AC) by monitoring the cerebrospinal fluid/serum albumin ratio and the volume transfer constant (K ). We showed that oral, but not intravenous, AC was associated with subsequent significant alteration in gut microbial composition and an increase in BBB permeability in all monkeys, especially in the thalamus area. Acetic and propionic acids might play a pivotal role in this newly found communication between the gut and the central nervous system. Antibiotic-induced gut microbial composition change, especially the decrease in acetic acid- and propionic acid-producing phyla and genera, might have a potential effect on the increase in BBB permeability, which may contribute to a variety of neurological and psychological diseases.
血脑屏障（BBB）有助于维持大脑内环境稳定。肠道微生物群组成影响啮齿动物 BBB 的发育和紧密连接蛋白的表达。然而，我们仍然不知道肠道微生物组成是否对正常成年动物的 BBB 通透性和功能有直接影响。在本研究中，我们通过监测脑脊液/血清白蛋白比值和体积转移常数（K ）来确定接受阿莫西林-克拉维酸（AC）的恒河猴 BBB 通透性的时空调变。我们表明，口服而非静脉注射 AC 与随后所有猴子的肠道微生物组成的显著改变以及 BBB 通透性的增加有关，尤其是在丘脑区域。乙酸和丙酸可能在肠道和中枢神经系统之间的这种新发现的通讯中发挥关键作用。抗生素诱导的肠道微生物组成变化，特别是产生乙酸和丙酸的菌门和属的减少，可能对 BBB 通透性的增加有潜在影响，这可能导致多种神经和心理疾病。
