Tonsillar Microbiota Alterations Contribute to Immune Responses in Psoriasis by Skewing Aged Neutrophils.

The interplay between microbiota and the onset of immune-mediated diseases is increasingly coming to light. However, the role of tonsillar microbiota in cutaneous inflammation remains largely unknown. We aimed to determine how tonsillar microbiota influence skin inflammation in psoriasis and to uncover the underlying molecular mechanisms. Tonsillar microbiota samples were collected from 24 healthy controls and 28 psoriasis patients. Microbial community composition was analyzed using 16S rRNA sequencing and metagenomic sequencing. Serum levels of short-chain fatty acids (SCFAs) were measured via liquid chromatography-mass spectrometry in 10 healthy controls and 14 psoriasis patients. Peripheral blood neutrophils from both groups were then exposed to a representative microbial metabolite, and key pro-inflammatory markers were evaluated using functional immune assays. We found significant alterations in the diversity and composition of the tonsillar microbial community in psoriasis group, with an increased prevalence of Bacteroidales and a decreased prevalence of Burkholderiales, Micrococcales, and Pasteurellales relative to healthy controls. Notably, a marked reduction in Rothia mucilaginosa correlated inversely with systemic inflammation (neutrophil-to-lymphocyte ratio) and disease severity (psoriasis area and severity index). Metagenomic analysis revealed disruptions in pathways critical for SCFAs production, including propanoate, pyruvate, and butanoate metabolism, which was supported by significantly lower serum SCFAs levels in psoriasis patients. Functional assays demonstrated that SCFAs inhibited neutrophil aging, pro-inflammatory cytokine secretion, and neutrophil extracellular traps (NETs) formation. Our findings reveal that changes in tonsillar microbiota and their metabolic outputs contribute to psoriasis by modulating immune responses, highlighting potential clinical implications.