Tonsillar microbiota alterations contribute to immune responses in psoriasis by skewing aged neutrophils

BACKGROUND: 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. OBJECTIVES: To determine how the tonsillar microbiota influences skin inflammation in psoriasis and to uncover the underlying molecular mechanisms. METHODS: Tonsillar microbiota samples were collected from 24 healthy control individuals and 28 patients with psoriasis. Microbial community composition was analysed with 16S rRNA and metagenomic sequencing. Serum levels of short-chain fatty acids (SCFAs) were measured via liquid chromatography-mass spectrometry in 10 healthy control participants and 14 patients with psoriasis. Peripheral blood neutrophils from both groups were then exposed to a representative microbial metabolite and key proinflammatory markers evaluated using functional immune assays. RESULTS: We found significant alterations in the diversity and composition of the tonsillar microbial community in patients with psoriasis, with an increased prevalence of Bacteroidales and a decreased prevalence of Burkholderiales, Micrococcales and Pasteurellales relative to healthy control participants. 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 to SCFA production, including propanoate, pyruvate and butanoate metabolism, which was supported by the significantly lower serum SCFA levels found in patients with psoriasis. Functional assays demonstrated that SCFAs inhibited neutrophil ageing, proinflammatory cytokine secretion and neutrophil extracellular trap formation. CONCLUSIONS: Our findings reveal that changes in tonsillar microbiota and their metabolic outputs contribute to psoriasis by modulating -immune responses, with potential clinical implications.