"肺与大肠相表里"的全生命周期代谢全景图谱:基于大鼠肺组织、血清与粪便样本的跨器官代谢调控研究OA

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 develop-mental 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 pediat-ric 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 differen-tial 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 sorbi-tol,while those in feces were mainly 17α,20α-dihydroxy-4-pregnene-3-one,4-hydroxyphenylacetic acid,and putrescine.Shared me-tabolites among all sample types included lactate,β-hydroxybutyrate,glycine,and glutamine.Significant differences in metabolic pro-files were observed between juvenile and adult rats across lung,serum,and fecal samples.KEGG pathway enrichment analysis re-vealed 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"meta-bolic axis may constitute the material basis of the TCM theory of"the lung and large intestine being internally-externally related",offer-ing new scientific insights for TCM-based diagnosis and metabolic intervention in pediatric respiratory diseases.