Xiaoer Chiqiao Qingre Granules (XECQ) is a traditional Chinese medicine (TCM) prescription officially recorded in the Pharmacopoeia of the People's Republic of China for pediatric use. It originated from classical TCM formulas such as “Yinqiao San” and evolved through clinical practice to specifically target pediatric febrile and respiratory disorders (Bao, 2025). According to TCM theory, XECQ is traditionally indicated for the treatment of wind-heat invasion and toxin accumulation, manifested as fever, sore throat, cough, yellow phlegm, and constipation—symptoms that closely correspond to the clinical presentations of AURTI in modern medicine (L. Zhao et al., 2025). This formulation is composed of fourteen herbs, including Glycine max (L.) Merr. (9.0 %), Forsythia suspensa (Thunb.) Vahl (12.0 %), Mentha canadensis L. (6.0 %), Glycyrrhiza uralensis Fisch. (5.0 %), Rheum palmatum L. (5.0 %), Nepeta cataria L. (6.0 %), Gardenia jasminoides J.Ellis (parched, 5.0 %), Artemisia caruifolia Buch.-Ham. ex Roxb. (9.0 %), Bupleurum chinense DC. (6.0 %), Areca catechu L. (4.0 %), Magnolia officinalis Rehd.et Wils. (9.0 %), Scutellaria baicalensis Georgi (9.0 %), Pinellia ternata (Thunb.) Ten. ex Breitenb. (9.0 %), and Paeoniae Radix Rubra (6.0 %). In traditional usage, these ingredients function synergistically to clear heat, detoxify, disperse wind, relieve sore throat, and promote bowel movement, thereby alleviating systemic febrile conditions and respiratory inflammation (Zeng et al., 2022).

Pharmacological investigations have demonstrated that XECQ exerts febrifugal, anti-inflammatory, analgesic, and aperient effects (Liu et al., 2023, Liu et al., 2023), aligning with its traditional therapeutic indications. Documented clinical efficacy exists for pediatric administration, particularly in treating juvenile pyrexia, cough, pharyngeal inflammation, and related upper respiratory afflictions (Mo et al., 2022). However, pediatric patients exhibit age-stratified physiological characteristics due to ongoing growth and maturation, which profoundly influence the disposition and pharmacodynamics of herbal medicines. Differences in body composition, organ development, and metabolic enzyme activity result in age-dependent variations in gastrointestinal absorption, tissue distribution, plasma protein binding, biotransformation, renal clearance, and therapeutic responses (Kouznetsova et al., 2022). While some progress has been made in ensuring the quality consistency of XECQ—such as identifying antioxidant constituents using four-wavelength fusion fingerprinting and ultraviolet spectral quantum fingerprinting (L.P. Zhao et al., 2025), and establishing optimized quality control methods via multi-wavelength fusion HPLC fingerprinting combined with chemometrics (Xu et al., 2020)—there remains a substantial knowledge gap. Specifically, XECQ-induced endogenous metabolic and microbiome alterations in pediatric versus adult patients with AURTI are poorly characterized, and the mechanistic basis for its pediatric efficacy has not been systematically elucidated. Bridging this gap is essential to provide scientific validation for its traditional use and to optimize evidence-based pediatric applications.

Metabonomic, a key tool in systems biology, offers a dynamic and sensitive approach to characterize phenotypic changes at the molecular level (Tasca et al., 2024). It is increasingly applied to investigate disease mechanisms and host–microbiota interactions. The intestinal microbiome and its metabolites are now recognized as pivotal regulators of host metabolism, immunity, and neurodevelopment (Li et al., 2024). From early infancy, the intestinal microbiome co-develops with the host, performing essential roles in energy metabolism, immune modulation, and neural development (Ovaska et al., 2024). Pediatric intestinal microbiome composition undergoes gradual maturation beyond age three, with delayed stabilization compared to adult microbiota (Xu and Wan, 2025), which may contribute to age-specific susceptibility to infectious diseases. AURTI, a leading cause of pediatric morbidity, has been linked to intestinal microbiome dysbiosis (Zhu et al., 2025). Evidence suggests that the microbiota shapes mucosal immunity and barrier integrity, while microbial metabolites act as signaling molecules modulating immune responses and offering novel therapeutic targets (Wang et al., 2025; Fu et al., 2024).

In this study, 3–4-week-old rats were selected to approximate the developmental stage of human children aged 2–12 years, based on comparative growth curves, organ maturation, and metabolic enzyme development (Lai et al., 2022a). By employing integrated metabolomic–microbiome profiling, we characterized XECQ-induced metabolic signatures and intestinal microbiome shifts in young rats, with adult rats serving as comparators. This approach enabled the identification of age-dependent regulatory patterns and clarified how XECQ ameliorates AURTI in immature organisms. Our findings provide mechanistic insights and preclinical evidence that directly support and scientifically validate the traditional pediatric use of XECQ for managing AURTI.