D3.231 - Gut Microbiome Dysbiosis in Antihistamine-Refractory Chronic Spontaneous Urticaria and Its Association with Disease Characteristics- A Cross-Sectional Case–Control Analysis

Chronic spontaneous urticaria (CSU) is an immune-mediated mast-cell disorder. Increasing evidence suggests that altered skin-gut axis may influence disease pathogenesis. This study aimed to compare gut microbiome composition between CSU patients inadequately controlled with second-generation H1-antihistamines (sgAHs) and healthy controls, and to evaluate associations with disease characteristics.

This cross-sectional case–control study included 20 CSU patients unresponsive to standard-dose sgAHs and 15 age- and sex-matched healthy controls. Clinical characteristics, disease duration, associated angioedema and inducible urticaria features, and treatment status were recorded. Stool samples were collected from all participants for microbial DNA extraction and 16S rRNA gene sequencing. Bioinformatic analysis was performed to assess microbial diversity, richness, and taxonomic composition.

CSU patients (mean age 39.5 ± 9.3 years; male: female 1:4) and controls (mean age 35 ± 13 years; male: female 1:2) were comparable in baseline demographics. The median duration of CSU was 42 months (interquartile range 7–81 months). Angioedema and symptomatic dermographism were present in 30% and 20% of patients, respectively. At inclusion, 60% of patients were receiving add-on anti-IgE therapy (omalizumab), while 40% were on up-dosed sgAHs.

Gut microbiome analysis revealed increased alpha diversity and microbial richness in CSU patients compared to healthy controls. CSU patients demonstrated reduced abundance of short-chain fatty acid–producing commensal bacteria and increased load of opportunistic pathogens. The Firmicutes/Bacteroidetes ratio was higher in the CSU group. Within CSU patients, higher relative abundance of Bacteroides and reduced Firmicutes were associated with greater disease activity and poorer disease control, independent of treatment modality.

Gut microbiome dysbiosis is seen in CSU and is linked with disease activity and control, suggesting a possible contributory role of gut microbiota–driven immune dysregulation in CSU pathophysiology.