Hsueh Mi-Yun, Jeng Mei-Jy, Chou Chia-Sui, Chang Chia-Wei, Zou Ciao-Ting
Institute of Emergency and Critical Care Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
Neonatal Medical Care Center, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Pediatr Res. 2025 Apr 9. doi: 10.1038/s41390-025-03924-2.
Early antibiotic exposure may disrupt gut microbiome and affect the gut-lung axis. We examined the impact of prolonged antibiotic exposure during early life on growth and subsequent acute lung injury (ALI) in a rat pup model.
Thirty-four 7-day-old rat pups were divided into Control, Antibiotics (Anti), Lung injury (LI), and Antibiotics-Lung Injury (Anti-LI) groups. The Anti and Anti-LI groups received oral Amoxicillin-Clavulanic acid from 7 to 40 days old, while Control and LI groups received sham water. ALI was induced in LI and Anti-LI groups with intratracheally administered lipopolysaccharide at 41 days old; all were sacrificed at 42 days old. Fecal bacterial sequencing, serum cytokine analysis, and pulmonary histological examination were performed.
Control and LI groups showed better weight gain from day 19 compared to Anti and Anti-LI groups. Anti and Anti-ALI groups exhibited decreased fecal microbial diversity (P < 0.05) and reduced Firmicutes abundance (P < 0.05) versus Control and LI groups. No significant difference in ALI severity was found between antibiotic-treated and non-treated groups.
Prolonged early-life antibiotic exposure in this rat pup model significantly reduced gut microbiota diversity and exhibited a non-significant trend toward lower weight gain, without exacerbating the severity of subsequent LPS-induced ALI.
Prolonged early-life antibiotic exposure decreased gut microbial diversity in rat pups. Antibiotics-exposed groups exhibited a trend of reduced weight gain compared to controls, although the difference was not statistically significant. Despite the observed alterations in the gut microbiota, there were no significant differences in the severity of subsequent acute lung injury between the groups with and without prolonged antibiotic exposure. The study findings advocate for a more judicious use of antibiotics in neonates, emphasizing that appropriate antibiotic stewardship is critical for preserving gut health and may also support growth.
早期抗生素暴露可能会破坏肠道微生物群并影响肠-肺轴。我们在幼鼠模型中研究了生命早期长期抗生素暴露对生长及随后急性肺损伤（ALI）的影响。
将34只7日龄幼鼠分为对照组、抗生素组（Anti）、肺损伤组（LI）和抗生素-肺损伤组（Anti-LI）。Anti组和Anti-LI组从7日龄至40日龄口服阿莫西林-克拉维酸，而对照组和LI组给予假处理的水。41日龄时，对LI组和Anti-LI组经气管内给予脂多糖诱导ALI；所有幼鼠在42日龄时处死。进行粪便细菌测序、血清细胞因子分析和肺组织学检查。
与Anti组和Anti-LI组相比，对照组和LI组从第19天起体重增加更好。与对照组和LI组相比，Anti组和Anti-ALI组粪便微生物多样性降低（P<0.05），厚壁菌门丰度降低（P<0.05）。抗生素治疗组和未治疗组之间ALI严重程度无显著差异。
在该幼鼠模型中生命早期长期抗生素暴露显著降低了肠道微生物群多样性，并呈现出体重增加较低的非显著趋势，而不会加重随后脂多糖诱导的ALI严重程度。
生命早期长期抗生素暴露降低了幼鼠肠道微生物多样性。与对照组相比，抗生素暴露组呈现出体重增加减少的趋势，尽管差异无统计学意义。尽管观察到肠道微生物群有改变，但长期抗生素暴露组和未暴露组之间随后急性肺损伤的严重程度无显著差异。研究结果提倡在新生儿中更明智地使用抗生素，强调适当的抗生素管理对于维护肠道健康至关重要，也可能有助于生长。
