Emerging evidence has shown that microbiota dysbiosis and aberrant bile acid (BA) profiles are correlated with disease progression. This study elucidates dysregulated BA metabolism in psoriasis patients and imiquimod-treated female mice, coupled with increased expression of the farnesoid X receptor (FXR) in keratinocytes. Activation of FXR by glycochenodeoxycholic acis (GCDCA) ameliorates psoriatic symptoms by enhancing lipid metabolism, particularly fatty acid oxidation. Mechanistically, the FXR-mediated enhancement of antioxidant capacity by upregulating NQO1 expression underlies its regulatory role in lipid metabolism, offering an insight into FXR's role in oxidative stress and lipid metabolism. Conversely, keratinocyte-specific FXR ablation exacerbates psoriasis severity. Gut microbiota dysbiosis is further identified as a pivotal contributor to perturbations in BA profiles in psoriasis. These preclinical findings support a mechanistic model linking gut microbiota dysbiosis and BA alterations to FXR signaling in keratinocytes and psoriasis-associated metabolic dysregulation, suggesting therapeutic potential for microbiota-targeted interventions.
Lian et al. (Mon,) studied this question.