An integrated metabolome-microbiome analysis revealed distinct regulatory effects of Xiaoer Chiqiao Qingre granules in young versus adult rats with acute upper respiratory tract infection.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoer Chiqiao Qingre Granules (XECQ), officially recognized in the Chinese Pharmacopoeia (Approval No. Z20123090), represent a widely used traditional Chinese medicine (TCM) formulation for treating acute upper respiratory tract infection (AURTI) across both pediatric and adult patients.

AIM OF THE STUDY: This investigation examined XECQ's divergent regulation of endogenous metabolism and intestinal microbiome in juvenile versus mature rats, serving clinical medication to support pediatric utilization of XECQ.

MATERIALS AND

METHODS

AURTI model was constructed, and serum inflammatory cytokine levels, pulmonary histopathology, and immunohistochemical analysis were assessed. Young rats served as pediatric developmental proxies. Integrated serum metabolomics and 16S rDNA sequencing methodologies elucidated XECQ's systemic modulatory actions upon host metabolism and enteric microbial communities.

RESULTS

XECQ manifested anti-AURTI efficacy across both age cohorts. Metabolites quantification identified 37 juvenile-specific and 18 adult-specific serum biomarkers. Additionally, XECQ modulated intestinal microbiome diversity and enhanced community richness across both age groups. Following XECQ treatment, the genera Subdoligranulum, Marvinbryantia, Anaerostipes, Bacillus, and Dubosiella_ag were significantly restored in young rats, while Escherichia-shigella, Parabacteroides, and Subdoligranulum showed notable recovery in adults. Species clustering analysis revealed distinct differences in intestinal microbiome modulation between age groups, with young rats exhibiting markedly different regulatory patterns for genera such as norank_f_Muribaculaceae, norank_f_Eubacterium_coprostanoligenes_group, Clostridium_sensu_stricto_1, and norank_f_Oscillospiraceae. In young rats, XECQ primarily regulated amino acid metabolism, notably pathways involving cysteine and methionine. In adult rats, the therapeutic effects were mainly associated with the modulation of pentose and glucuronate interconversion and purine metabolic pathways. Notably, glycerophospholipid metabolism emerged as a shared pathway across both age groups under normal conditions, during AURTI pathology, and following XECQ treatment.

CONCLUSION

XECQ differentially modulates the serum metabolome and intestinal microbiome between young and adult rats, highlighting the necessity of pediatric-specific studies to support the clinical application of XECQ in children.