Early postnatal intervention with Bifidobacterium and Lactobacillus modulates short- and long-term glycolipid metabolism in mice through differential mechanisms

The early postnatal period represents a critical window for metabolic programming. Based on our previously established antibiotic-exposure model, this study investigated whether post-antibiotic supplementation with two infant-derived probiotic strains, Bifidobacterium breve 207-1 and Lacticaseibacillus paracasei 207-27, could differentially modulate short- and long-term glycolipid metabolism. Neonatal mice received antibiotics from postnatal day 0–14, followed by probiotic supplementation until weaning and subsequent high-fat diet challenge until adulthood. The antibiotic-treated groups were used as references to evaluate probiotic effects. B. breve 207-1 was more closely associated with additional lipid-related benefits in adulthood, potentially involving gut microbiota structure metabolic programming and ingWAT metabolic programming. These effects were characterized by reduction of Colidextribacter and Peptococcus , upregulation of unidentified Lachnospiraceae and Limosilactobacillus , downregulation of intestinal fatty acid transport-related genes, and an ingWAT browning-associated molecular profile. In contrast, L. paracasei 207-27 showed glucose-related benefits at both weaning and adulthood, which were associated with gut microbiota structure metabolic programming marked by enrichment of Lactobacillaceae -related taxa, suppression of Rikenellaceae RC9 gut group , Colidextribacter , and Anaerovorax , and regulation of metabolic hormones such as FGF21 and GLP-1. Neither probiotic strain further enhanced iBAT thermogenic programming relative to antibiotic exposure alone. These findings suggest that early postnatal probiotic intervention following microbiota perturbation exerts strain-specific metabolic effects and may inform precision probiotic strategies for metabolic programming.