Abstract To evaluate the effect of montelukast combined with inhaled corticosteroids (ICS) on the microbiome-metabolism-immunity 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 = 50 in the combination group and n = 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) (βᵢnt = −10. 24 ppb, 95% CI −16. 37 to −4. 11, P = 0. 001), Childhood Asthma Control Test (C-ACT) score (βᵢnt = +1. 83, P 0, q 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.
Fan et al. (Mon,) studied this question.