Prolonged early-life antibiotic exposure alters gut microbiota but does not exacerbate lung injury in a rat pup model.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Impact: 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.