Wan Qun, Cheng Ru-Yue, Guo Jia-Wen, Wang Ke, Shen Xi, Pu Fang-Fang, Li Ming, He Fang
Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2018 Apr;20(4):318-325. doi: 10.7499/j.issn.1008-8830.2018.04.013.
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.
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.
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).
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.
探讨头孢曲松对生命早期小鼠肠上皮及微生物群的影响,以及成年小鼠肠上皮的恢复和肠道微生物群的重建情况。
将36只BALB/C新生小鼠随机分为对照组和实验组,每组18只。实验组小鼠在出生后21天内每天经口灌胃给予头孢曲松100 mg/kg。对照组小鼠经口灌胃给予等体积的生理盐水。采用免疫组织化学法检测肠上皮中Ki67、Muc2和ZO-1的表达。采用qPCR和二代测序技术分析粪便细菌的总体浓度和组成。
头孢曲松干预21天后,实验组小鼠体重显著降低,肠上皮细胞中Ki67和ZO-1的表达显著降低,Muc2的表达显著升高,粪便细菌总体浓度显著降低,粪便细菌多样性显著增加,与对照组相比差异有统计学意义(P<0.05)。厚壁菌门是实验组最常见的粪便细菌类型,其中葡萄球菌和肠球菌数量较多。实验组肠上皮有一定程度的恢复,但出生后56天时两组小鼠体重和肠道微生物群结构仍存在显著差异(P<0.05)。
早期头孢曲松干预显著影响生命早期肠上皮的发育和肠道微生物群的构建。生命早期肠道微生物群的损伤可能持续到成年期,影响生长发育和生理代谢。