<i>Lactobacillus paragasseri</i> LG‐1 Alleviates Urticaria‐Like Symptoms in Mice via Modulation of Gut Microbiota, Hypoxanthine and Uric Acid

Chronic Spontaneous Urticaria (CSU) is an immunoinflammatory disorder with complex pathogenesis. Emerging evidence implicates that gut microbiota dysbiosis plays a pivotal role in this pathological network. Integrated 16S rRNA sequencing and untargeted metabolomics revealed distinct CSU-associated signatures, including significant reductions in Lactobacillus abundance and elevated serum uric acid (UA) and hypoxanthine levels. Functional screening identified Lactobacillus paragasseri LG-1 from breast milk as a potent purine-metabolising strain, demonstrating significant hypoxanthine and UA degradation in vitro. In an ovalbumin (OVA)-induced urticaria murine model, LG-1 administration demonstrated marked reductions in serum UA and hypoxanthine concentrations, alleviated clinical manifestations, and suppressed inflammation via TLR4-NF-κB pathway inhibition. Moreover, it modulated gut microbial composition by promoting Lactobacillus proliferation while restraining pathogenic bacteria. These findings collectively established that LG-1 exerted dual therapeutic effects through uric acid/hypoxanthine degradation and microbiome remodelling. Our study provides compelling evidence for microbiome-targeted strategies in CSU management, highlighting LG-1 as a promising therapeutic candidate.