To evaluate the effect of montelukast combined with inhaled corticosteroids (ICS) on the microbiomemetabolismimmunity axis in children with asthma and to quantify the mediating role of short-chain fatty acids, this single-center, randomized controlled trial enrolled 100 asthmatic children (aged 6.11) who received inhaled corticosteroids with or without montelukast for 12 weeks (n 5 50 in the combination group and n 5 50 in the ICS-alone group). Microbiome profiles from nasal and fecal samples were assessed via 16S sequencing, and short-chain fatty acids (SCFAs) were quantified by LC-MS/MS. Immune markers (Tregs, cytokines) were measured by flow cytometry and Bio-Plex. Efficacy analyses employed linear mixed-effects models, and SCFA mediation was tested using bootstrap analysis. The combination group demonstrated significantly greater improvements in clinical outcomes including fractional exhaled nitric oxide (FeNO) (ß_int 5 - -10.24 ppb, 95% CI -16.37 to  -4.11, P 5 0.001), Childhood Asthma Control Test (C-ACT) score (ß_int 5 t1.83, P < 0.05) and FEV1% (ß_int 5 t1.87, P < 0.05) compared to ICS alone. Microbiome analysis revealed enhanced a-diversity in both nasal and fecal samples (interaction P < 0.01) with significant community structure changes (PERMANOVA interaction P_perm < 0.01). Specific genus-level alterations included reduced nasal Moraxella and Haemophilus (logFC < 0, q < 0.10) and increased fecal SCFA-producing taxa including Faecalibacterium, Roseburia, Subdoligranulum, Agathobacter, and Eubacterium hallii group (logFC > 0, q < 0.10). The combination therapy also led to elevated fecal and serum SCFA levels ( ß_int > 0, P < 0.01), enhanced regulatory T cell (Treg) and IL-10 responses, and suppressed Th2 cytokines (IL-4/IL-5/IL-13). Mediation analysis confirmed SCFAs partially mediated FeNO improvement, with proportions of 30.0% for total SCFAs and 37.5% for butyrate (ACME and ADE both negative, P < 0.01). The combination of montelukast and inhaled corticosteroids was superior to inhaled corticosteroids alone, providing clinical benefits that were linked to favorable remodeling of the airway-gut microbiome and enhanced Treg/IL-10 immunity. This improvement was partially mediated by short-chain fatty acids, with a comparable safety profile.  Kulcsszavak: children with asthma, montelukast, short-chain fatty acids, gut.lung axis