Fig. 1: CSU comes with reduced gut microbiome diversity, lower levels of SCFA-producing gut bacteria, higher levels of conditional pathogenic gut bacteria, decreased blood levels of SCFAs, and increased blood levels of LPS, which drive disease relapse.

a PCoA presents β-diversities based on Bray–Curtis dissimilarity determined by PERMANOVA, and α-diversity by Shannon and Simpson indices. HC vs CSU. b The 15 differential species identified by MaAsLin2 with BH correction. ^#P < 0.2, ⁺P < 0.1, *P < 0.05, **P < 0.01. c Comparison of SCFA-producing bacteria between HC and CSU. d Abundance of acetate, propionate, and caproate through targeted metabolomics. e Spearman’s correlation between SCFAs and differential species. f Spearman’s correlation between differential species and clinical characteristics of CSU. The blocks in red or blue denote positive and negative correlation, respectively. The color gradient represents the strength of correlation. g Abundance of opportunistic pathogens was compared between HC and CSU. h LPS-related metabolic pathways and comparison of LPS level between HC and CSU. i Spearman’s correlations between plasma LPS and sum of SCFA-producing bacteria or opportunistic pathogens. The line represents center of overall linear fit, with gray areas standing for the standard error of 95% confidence interval. j Relapse-free analysis based on the 15 differential species or plasma LPS by log-rank test. The data are presented as mean ± SEM. P values were provided in Source Data File for b, e, and f. Two-tailed Wilcoxon test were used for a right, c, g right and h left. Two-tailed t tests were used for d, h right. The shape and whiskers of violin plot respectively represent density distribution and overall range of the data in a and b. The center and bounds of box respectively represent median, the lower quartile (Q1) and the upper quartile (Q3) were in a–c, g, and h. The whiskers denote the lower quartile minus 1.5 times the IQR and the upper quartile plus 1.5 times the IQR in c, g and h. SCFAs short-chain fatty acids, HC healthy controls, CSU chronic spontaneous urticaria, BMI body mass index, UAS7 weekly urticaria activity score, DLQI Dermatology Life Quality Index, UCT Urticaria Control Test. Source data are provided as a Source Data file.