Gut microbiota-induced perturbations in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasis

ABSTRACT: Emerging evidence has shown that microbiota dysbiosis and aberrant bile acids (BAs) profiles are correlated with disease progression. This study elucidates dysregulated BAs 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 acid (GCDCA) ameliorates psoriatic symptoms by enhancing lipid metabolism, particularly fatty acid oxidation. Mechanistically, the FXR-mediated enhancement of antioxidant capacity by upregulating NAD(P)H quinone dehydrogenase 1 (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 findings support a mechanistic model linking gut microbiota and BA alterations to FXR signaling in keratinocytes and psoriasis-associated metabolic dysregulation, suggesting therapeutic potential for microbiota-targeted interventions.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse-phase

PROVIDER: MTBLS14183 | MetaboLights | 2026-03-29

REPOSITORIES: MetaboLights