OBJECTIVE Based on the traditional Chinese medicine (TCM) theory of "the lung and large intestine being internally-externally related", to systematically characterize metabolic changes in the lung, serum, and feces of rats at different developmental stages and analyze their intrinsic connections employing non-targeted metabolomics, aiming to elucidate the material basis of the "gut-blood-lung" metabolic axis and provide experimental evidence for metabolic intervention and TCM-based treatment of pediatric respiratory diseases.

METHODS Gas chromatography-mass spectrometry (GC-MS) was used to detect metabolites in lung tissue, serum, and fecal samples from rats aged 3, 7, 12, 24, 56 and 70 weeks. Principal component analysis (PCA) and variable importance in projection (VIP) screening were conducted to identify key metabolites. Common metabolites among the three sample types and differential metabolites between juvenile (3-week-old) and adult (7-week-old) rats were further analyzed.

RESULTS High-VIP metabolites in lung tissue and serum included β-glycerophosphate, glucose-1-phosphate, maltose, xanthine, hypoxanthine, lauric acid, and sorbitol, while those in feces were mainly 17α, 20α-dihydroxy-4-pregnene-3-one, 4-hydroxyphenylacetic acid, and putrescine. Shared metabolites among all sample types included lactate, β-hydroxybutyrate, glycine, and glutamine. Significant differences in metabolic profiles were observed between juvenile and adult rats across lung, serum, and fecal samples. KEGG pathway enrichment analysis revealed that taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and arginine and proline metabolism were highly impacted in juvenile lung and serum, while alanine, aspartate and glutamate metabolism, starch and sucrose metabolism, and arginine biosynthesis were predominant in feces.

CONCLUSION The metabolic characteristics of the lung, blood, and intestine exhibit distinct age-dependent patterns, with amino acid and energy metabolism being more active during the juvenile stage, reflecting the high metabolic demands of tissue development and immune homeostasis. These dynamic changes in the "gut-blood-lung" metabolic axis may constitute the material basis of the TCM theory of "the lung and large intestine being internally-externally related", offering new scientific insights for TCM-based diagnosis and metabolic intervention in pediatric respiratory diseases.