Objective: To explore the effect of lead exposure on the neurobehavior and gut microbiota community structure in mice. Methods: In August 2019, 64 C57BL/6 mice were randomly divided into 4 groups: control group (0 ppm) , low lead exposure group (20 mg/l) , medium lead exposure group (100 mg/l) and high lead exposure group (500 mg/l) . During the experiment, they were free to eat and drink. The drinking water of the lead exposure group was mixed with lead acetate, and sodium acetate was added in the control group. After 10 weeks of exposure, the Morris water maze was used to test the learning and memory ability of each group of mice, and then they were sacrificed for sampling. ICP-MS was used to detect lead content in whole blood and brain tissue. ELISA was used to determine the level of IL-1β in mouse serum. 16S rRNA sequencing was used to detect the structural diversity of the intestinal flora in feces, and then the correlation between the flora and behavior indicators was analyzed. Results: In the Morris water maze experiment, compared with the control group, there was no significant difference in the body weight and swimming speed of the mice in the lead exposure groups. The escape latency of the mice in the 100 mg/l and 500 mg/l dose groups was prolonged, and the number of platform crossings decreased (P<0.05) ; meanwhile, the staying time of the mice in the 500 mg/l Pb-treated group in the target quadrant was lower than that of the control group, and the difference was statistically significant (P<0.05) . Compared with the control group, the blood lead content of the mice in each lead exposure group was significantly increased, and the brain lead content of mice in the 500 mg/l dose group was significantly elevated (P<0.05) . The serum IL-1β levels of mice in each lead exposure group were higher than those of the control group (P<0.05) . At the phylum level, the relative abundance of the Proteobacteria phylum in all of Pb-treated groups was significantly increased (P<0.05) ; at the genus level, Allobaculum, Desulfovibrio, Lachnospiraceae_NK4A136_group, Turicibacter and Ureaplasma were significantly increased (P<0.05) . Among them. The relative abundance of Desuffaoibrio, Turici bacter, and Ureaplasma was negatively correlated with the residence time of mice in the quadrant of the platform (r=-0.32, -0.29, -0.44, P<0.05) . Conclusion: Lead exposure induced learning and memory impairments in mice, which may be related to the disturbance of the gut microbiota.
目的： 探讨铅暴露对小鼠神经行为、肠道菌群群落结构的影响及其相关关系。 方法： 于2019年8月，将64只4周龄C57BL/6小鼠随机分为对照组，低、中、高铅暴露组，每组16只。实验期间自由摄食饮水，低、中、高铅暴露组分别在饮用水中加入20、100和500 mg/l醋酸铅，对照组添加同量的醋酸钠。暴露10周后，Morris水迷宫检测小鼠学习记忆能力，随后处死取样，采用ICP-MS检测血铅和脑铅含量，ELISA法检测血清中白介素-1β（IL-1β）水平，16S rRNA测序检测粪便中肠道菌群改变，使用Pearson相关系数法对菌群和行为学指标进行相关性分析。 结果： Morris水迷宫实验显示，与对照组比较，各铅暴露组小鼠体重和游泳速度无明显差异，中、高铅暴露组小鼠的逃避潜伏期延长，平台穿越次数减少，差异有统计学意义（P<0.05）；高铅暴露组小鼠在目的象限停留时间低于对照组和其他剂量组，差异均有统计学意义（P<0.05）；小鼠的血铅含量随着铅暴露剂量升高而增加，高铅暴露组小鼠脑铅含量与其他组比较明显升高（P<0.05）；各铅暴露组小鼠血清中IL-1β水平高于对照组（P<0.05）；各铅暴露组小鼠均发生肠道菌群紊乱，在门水平上，变形菌门的相对丰度明显升高（P<0.05），在属水平上，别样棒菌属、脱硫弧菌属、毛螺菌属、苏黎世杆菌属和脲原体属均明显增加（P<0.05）；脱硫弧菌属、苏黎世杆菌属和脲原体属的相对丰度与小鼠在平台所在象限的停留时间呈负相关关系（r=-0.32、-0.29、-0.44，P<0.05）。 结论： 铅暴露引起小鼠学习记忆能力的损伤，可能与铅暴露导致小鼠的肠道菌群紊乱有关。.
Keywords: Gut microbiota; Lead; Learning and memory.