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<p>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&#xa0;dysbiosis and BA alterations to FXR signaling in keratinocytes and psoriasis-associated metabolic dysregulation, suggesting therapeutic potential for microbiota-targeted interventions.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月18日

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  • Panpan Lian,
  • Renwei Lu,
  • Chaode Gu,
  • Junaid Wazir,
  • Wentong Wang,
  • Yangyongyi Zong,
  • Yun Xia,
  • Jie Ni,
  • Huimei Chen,
  • Enrico Petretto,
  • Eckardt Treuter,
  • Rongrong Fan,
  • Airong Yang,
  • Zhonglan Su,
  • Hongwei Wang,
  • Zhiqiang Huang

摘要

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.