Abstract

Background Refractory asthma in children remains a clinical challenge despite conventional therapies, with emerging evidence linking gut microbiome dysbiosis to persistent inflammation via the gut-lung axis. This study investigated whether multi-strain probiotic supplementation could improve asthma control and restore microbial balance when added to standard treatment. Methods This prospective randomized controlled trial enrolled 88 children aged 4–8 years with refractory asthma. Participants were allocated into two groups (n = 44 each): a conventional treatment group (bronchodilators and glucocorticoids) and a combination treatment group, which received conventional therapy plus a multi-strain probiotic (Bifidobacterium, Lactobacillus acidophilus, Streptococcus thermophilus) for 4 months. Primary outcomes were asthma control level, Asthma Control Test (ACT) scores, and pulmonary function (FEV₁, FVC, PEF). Secondary outcomes included gut microbiota changes, assessed by 16S rRNA gene sequencing. Results Combination therapy achieved complete asthma control in 68.18% of patients versus 36.36% with conventional therapy (Z = 2.415, p < 0.05). Post-treatment ACT scores were higher in the combination group (22.45 ± 1.20 vs. 19.78 ± 1.45; p < 0.05), with superior improvements in FEV1 (2.65 ± 0.10 L vs. 2.30 ± 0.08 L; p < 0.001), FVC (3.10 ± 0.18 L vs. 2.80 ± 0.15 L; p < 0.001), and PEF (4.00 ± 0.25 L/s vs. 3.50 ± 0.20 L/s; p < 0.001). Symptoms resolved faster with combination therapy (e.g., cough: 5.60 ± 1.50 vs. 10.45 ± 2.30 days; p < 0.05). Microbiome analysis showed increased alpha diversity (e.g., Shannon index: p < 0.05) and beneficial shifts in the combination group, including higher Bifidobacterium (25.00 ± 15.31% vs. 0.98 ± 1.92%; p < 0.001) and reduced Bacteroides, with distinct beta diversity clustering (PERMANOVA p < 0.05).