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[Effect of ceftriaxone on the intestinal epithelium and microbiota in neonatal mice]
Qun Wan1, Ru-Yue Cheng, Jia-Wen Guo
1Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China. nrb47389@nifty.com.
Insights
Early ceftriaxone exposure in mice disrupts intestinal development and microbiota, with lasting effects into adulthood. This early-life antibiotic intervention impacts gut health and overall growth.
Area of Science:
- Microbiology
- Developmental Biology
- Pharmacology
Background:
- Early-life antibiotic exposure can have long-term consequences on host-microbe interactions.
- The intestinal epithelium and microbiota undergo critical development during the early-life stage.
Purpose of the Study:
- To investigate the effects of ceftriaxone on the developing intestinal epithelium and microbiota in neonatal mice.
- To assess the long-term recovery of the intestinal epithelium and microbiota in adult mice following early-life ceftriaxone exposure.
Main Methods:
- Neonatal BALB/C mice received daily ceftriaxone (100 mg/kg) or saline for 21 days.
- Immunohistochemistry assessed intestinal epithelial markers (Ki67, Muc2, ZO-1).
- qPCR and next-generation sequencing analyzed fecal bacterial concentration and composition.
Main Results:
- Ceftriaxone-treated mice showed reduced body weight, decreased Ki67 and ZO-1 expression, and increased Muc2 expression.
- Fecal bacterial concentration decreased, while diversity increased, with a shift in composition (e.g., increased Firmicutes, Staphylococcus, Enterococcus).
- Some recovery was observed by adulthood, but significant differences in body weight and microbiota structure persisted.
Conclusions:
- Early-life ceftriaxone significantly impacts intestinal epithelium development and microbiota construction.
- Disruption of the intestinal microbiota in early life may lead to persistent effects on growth and metabolism in adulthood.
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.
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