Gut and skin microbial dysbiosis correlate with systemic inflammation and pruritus in immunological non-responders

Introduction Among people living with human immunodeficiency virus (PLWH), those who exhibit immunological non-responders (INR) are highly susceptible to developing pruritus. The aim of this study was to examine the relationships among pruritus, alteration of the gut and skin microbiomes, and systemic inflammation in PLWH with INR. Methods Thirty-three PLWH with INR were enrolled and divided into Pruritus ( n = 18) and Control ( n = 15) groups. All participants met the defining criterion of a low CD4+ T cell count ( ≤ 350 cells/μl). We performed 16S rRNA gene sequencing of fecal and skin samples, and measured plasma IL-1β and IL-10 levels. Results Microbiome analysis revealed specific, bidirectional patterns of microbial dysbiosis. Specifically, the skin microbiome of the Pruritus Group exhibited significantly greater microbial richness (Chao1 and Faith's Phylogenetic Diversity indices, P < 0.01), coupled with significantly lower representation of the potentially protective genus Bacillus ( adjusted P < 0.05 ), compared with that of the INR Control Group. Conversely, the gut microbiome of the Pruritus Group exhibited significantly lower alpha diversity (adjusted P < 0.05) . Furthermore, we identified a significant positive correlation between levels of plasma pro-inflammatory cytokine IL-1β and the relative abundance of the opportunistic gut genus Veillonella ( adjusted P < 0.05 ). Conclusions Pruritic PLWH-INRs exhibit skin microbial hyper-richness, Bacillus depletion, and reduced gut diversity, suggesting a systemic inflammatory basis linked to gut-skin dysbiosis. These findings provide new insights into the pathological process, offering a potential foundation for future microbiome-targeted therapeutic strategies as novel management avenues.