Prevotella copri Exacerbates Psoriasis Through Keratinocyte‐Neutrophil Crosstalk via NF ‐ κB Activation

Psoriasis is a chronic inflammatory skin disorder driven by systemic immune dysregulation and recent studies have implicated the gut-skin axis in its pathogenesis. However, the specific role of individual gut microbes remains poorly understood. In this study, the impact of Prevotella copri (P. copri) on psoriasis development was examined and the underlying mechanisms were investigated. In an imiquimod (IMQ)-induced mouse model, oral administration of P. copri exacerbated skin inflammation, increased epidermal thickness, promoted neutrophil infiltration and aggravated disease severity. In vitro, stimulation with P. copri enhanced keratinocyte proliferation and pro-inflammatory responses, thereby activating co-cultured neutrophils. These effects were associated with activation of the NF-κB signalling pathway, as evidenced by increased phosphorylation of p65 and upregulation of inflammasome components. The inhibition of NF-κB signalling attenuated P. copri-induced keratinocyte hyperproliferation, neutrophil activation and inflammatory cytokine production. Our findings suggest that P. copri promotes psoriasis progression via NF-κB-mediated keratinocyte-neutrophil crosstalk, potentially through a gut-derived systemic inflammatory mechanism. Targeting the gut-skin axis and NF-κB pathway may offer new therapeutic opportunities for psoriasis.