Skin microbiome signatures track uremic pruritus severity in hemodialysis patients

Chronic kidney disease-associated pruritus (CKD-aP) is frequent in patients receiving maintenance hemodialysis and is often difficult to control. While systemic drivers are recognized, how the chronically altered skin microenvironment and its microbiome relate to itch severity remains insufficiently defined. In this single-center study, hemodialysis patients and healthy controls underwent pooled skin microbiome profiling by full-length 16 S rRNA sequencing, with differential taxa, functional features, and clinical associations analyzed using multivariate and correlation-based approaches. Compared with healthy controls, hemodialysis patients showed higher skin microbial richness and a distinct overall community structure. Within the dialysis cohort, increasing pruritus burden coincided with compositional turnover and depletion of canonical commensals. Machine learning and LEfSe highlighted pruritus-associated species-level signatures, with Propionibacterium sp. LG among the most informative features and Epilithonimonas hominis recurring across models. Network analysis indicated progressive fragmentation with greater pruritus severity, reflected by reduced connectivity and increased modularity. Predicted functional profiles suggested dialysis-associated alterations in microbial functional potential, with higher predicted representation of lipid biosynthesis pathways and lower predicted representation of core energy and nucleotide metabolism; pruritus severity was further linked to reductions in aerobic/energy-related functions. Phenotype prediction indicated higher inferred stress-tolerant and potentially pathogenic traits in pruritic patients. Taken together, hemodialysis was associated with broad skin microbiome remodeling, and worsening CKD-aP was accompanied by commensal loss, disrupted microbial interaction networks, and predicted functional shifts consistent with a more stress-adapted community. These features may reflect responses to the altered pruritic skin environment and provide microbiome-informed biomarkers and hypotheses for future mechanistic studies in CKD-aP.