Targeting the “gut-immune axis”: <em>Bifidobacterium longum</em> subsp. <em>infantis</em> CCFM111 serves as a novel therapeutic for pediatric allergic rhinitis

Perennial allergic rhinitis (PAR) is a chronic nasal inflammatory disease that significantly impairs children’s quality of life. Probiotics, capable of restoring microbial balance and modulating immunity, have emerged as promising adjunctive therapies, though evidence in PAR remains limited. In this 20-week randomized, double-blind, placebo-controlled trial, 182 children aged 3-12 years with PAR received either <em>Bifidobacterium longum</em> subsp. <em>infantis</em> CCFM111 (5 × 10⁹ CFU/day, administered as one sachet daily; n = 122) or placebo (maltodextrin; n = 60). After 8 weeks, the probiotic group was further randomized into a short-term subgroup and a long-term subgroup to evaluate the durability of therapeutic effects after probiotic discontinuation. The short-term subgroup (n = 60) discontinued supplementation and received placebo thereafter, whereas the long-term subgroup (n = 62) continued probiotic intake until week 20. The primary outcome was the change in the average modified combined symptom and medication score (ΔmCSMS) from baseline to weeks 7–8. Results showed that at week 8, probiotic treatment significantly reduced ΔmCSMS scores (<em>P</em> &lt; 0.001) and improved immune parameters compared with placebo. In the short-term subgroup, symptom improvement persisted for approximately 10 weeks after discontinuation of probiotics; however, by week 20 (12 weeks post-discontinuation), symptom scores had significantly relapsed compared with the long-term subgroup (<em>P</em> &lt; 0.01). Gut microbiota analysis revealed enrichment of <em>Romboutsia</em> and <em>Fusicatenibacter</em> and enhanced tryptophan metabolism, with increased indole derivatives associated with symptom relief, indicating that CCFM111 may exert its effects through the gut microbiota–tryptophan metabolism axis. No adverse events were observed. These findings suggest that CCFM111 may serve as a safe and effective adjunctive therapy for PAR in children. Trial registration: This study was registered on the website of www.chictr.org.cn, number ChiCTR2500095385.