Objective: To investigate the effect of ceftriaxone on the intestinal epithelium and microbiota in mice in the early-life stage, as well as the recovery of the intestinal epithelium and reconstruction of intestinal microbiota in adult mice.
Methods: A total of 36 BALB/C neonatal mice were randomly divided into control group and experimental group, with 18 mice in each group. The mice in the experimental group were given ceftriaxone 100 mg/kg every day by gavage within 21 days after birth. Those in the control group were given an equal volume of normal saline by gavage. Immunohistochemistry was used to measure the expression of Ki67, Muc2, and ZO-1 in the intestinal epithelium. qPCR and next-generation sequencing were used to analyze the overall concentration and composition of fecal bacteria.
Results: After 21 days of ceftriaxone intervention, the experimental group had a significant reduction in body weight, a significant reduction in the expression of Ki67 and ZO-1 and a significant increase in the expression of Muc2 in intestinal epithelial cells, a significant reduction in the overall concentration of fecal bacteria, and a significant increase in the diversity of fecal bacteria compared with the control group (P<0.05). Firmicutes was the most common type of fecal bacteria in the experimental group, and there were large amounts of Staphylococcus and Enterococcus. The experimental group had a certain degree of recovery of the intestinal epithelium, but there were still significant differences in body weight and the structure of intestinal microbiota between the two groups at 56 days after birth (P<0.05).
Conclusions: Early ceftriaxone intervention significantly affects the development of the intestinal epithelium and the construction of intestinal microbiota in the early-life stage. The injury of the intestinal microbiota in the early-life stage may continue to the adult stage and affect growth and development and physiological metabolism.
目的: 探究头孢曲松对生命早期小鼠肠道上皮组织及肠道菌群的影响，以及对成年期小鼠肠上皮组织恢复及菌群再建的影响。
方法: 36只BALB/C新生小鼠随机分为对照组和实验组（n=18）。实验组小鼠在出生后21 d内，每日用头孢曲松（100 mg/kg）灌胃，对照组用等量生理盐水灌胃。采用免疫组化法检测小鼠肠道各部位上皮细胞相关蛋白（Ki67、Muc2、ZO-1）表达；qPCR和二代测序法分析小鼠粪便细菌总浓度及粪便细菌组成。
结果: 头孢曲松干预21 d时，与对照组比较，实验组小鼠体重、肠上皮细胞相关蛋白Ki67、ZO-1表达降低，Muc2表达升高（P < 0.05）；总细菌浓度下降但丰富度及多样性增高（P < 0.05）；粪便细菌以厚壁菌门为主，含较多葡萄球菌和肠球菌。生后56 d时，实验组小鼠肠道上皮组织有所恢复，但体重、菌群群落结构等仍和对照组比较差异有统计学意义（P < 0.05）。
结论: 早期头孢曲松干预能显著损伤机体早期肠道上皮组织的发育和肠道菌群的构建，肠道菌群在生命早期的损伤会部分地延续到成年期，有可能继续影响机体在成年期各种生长发育及生理代谢。