Gut Microbiota Dysbiosis-driven Bile Acid Dysfunction Alters Keratinocyte Lipid Metabolism via FXR-NQO1 Signaling in Psoriasis

Gut Microbiota Dysbiosis-driven Bile Acid Dysfunction Alters Keratinocyte Lipid Metabolism via FXR-NQO1 Signaling in Psoriasis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Gut Microbiota Dysbiosis-driven Bile Acid Dysfunction Alters Keratinocyte Lipid Metabolism via FXR-NQO1 Signaling in Psoriasis Zhiqiang Huang, Panpan Lian, Renwei Lu, Junaid Wazir, Chaode Gu, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6337099/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Emerging evidence has shown that microbiota dysbiosis and aberrant bile acid (BA) profiles correlates with disease progression. However, it’s role in psoriasis progression remains unclear. This study elucidates dysregulated BA metabolism in psoriasis patients and imiquimod-treated mice, coupled with increased expression of the farnesoid X receptor (FXR) in keratinocyte. FXR activation with 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 a new insight into FXR’s role in oxidation stress and lipid metabolism. Conversely, keratinocyte-specific FXR ablation exacerbates psoriasis severity. Gut microbiota dysbiosis is further identified as a pivotal contributor to perturbed the profile of BA in psoriasis. These findings establish the gut microbiota-BA-FXR axis as a critical pathway in psoriasis pathogenesis and suggest probiotics/prebiotics as viable therapeutic interventions. Biological sciences/Physiology/Metabolism/Fat metabolism Health sciences/Diseases/Skin diseases/Vitiligo Full Text Additional Declarations There is NO Competing Interest. Supplementary Files 3.SupplementalmaterialsLianetal.pdf FXR function in keratinocytes Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6337099","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":447647741,"identity":"03dce4a6-c8c3-4477-b40f-75c6a7e90407","order_by":0,"name":"Zhiqiang 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