Early-Life Antibiotic Cocktail Intervention Alters Cecal Microbiota Composition and Metabolic Profiles in Suckling Rats

The early-life lactational window is critical for gut microbial colonization, intestinal maturation, and long-term host metabolic and immune programming. Although antibiotic-induced microbiota perturbation models are widely applied to investigate microbiota function, the overall microbiota perturbation efficiency and comprehensive metabolic alterations induced by broad-spectrum antibiotics during the lactational stage remain poorly characterized. In this study, neonatal SD rat pups were continuously administered a broad-spectrum antibiotic cocktail to establish a lactational antibiotic-perturbed dysbiosis model. The early-life antibiotic intervention induced mild impairment of the intestinal structure and significantly increased the relative hindgut weight. 16S rRNA sequencing demonstrated significant reductions in microbial α-diversity, profound remodeling of gut microbial communities, extensive depletion of core beneficial genera including Akkermansia, Bifidobacterium, and Lactobacillus, and significant enrichment of opportunistic pathogens. Untargeted metabolomics further revealed widespread cecal metabolic perturbations following antibiotic-induced microbiota perturbation, including decreased biosynthesis of microbiota-derived vitamins, and comprehensive disorders in lipid, tyrosine, pteridine, and steroid hormone metabolism. Collectively, this study systematically characterized the microbiota perturbation efficiency and multiomic metabolic phenotypes of antibiotic-induced microbiota perturbation in suckling rats, clarifying the regulatory effects of lactational microbial perturbation on intestinal microecology and host metabolic homeostasis. These findings provide fundamental phenotypic data for the application of early-life antibiotic-perturbed dysbiosis models and further mechanistic exploration of host–microbe crosstalk during the critical developmental window.