Peer-reviewedCC BY-NC-NDNature Communications
Gut microbiota-induced perturbation in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasis
11 affiliations
- 1Department of Dermatology, The First Affiliated Hospital, Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, P. R. China
- 2State Key Laboratory of Pharmaceutical Biotechnology, State Key Laboratory of Analytical Chemistry for Life Science, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, P. R. China
- 3Department of Dermatology, First Affiliated Hospital, Nanjing Medical University, Nanjing, P. R. China
- 4Suqian Scientific Research Institute of Nanjing University Medical School, Suqian, P. R. China
- 5Technique Center, Jinling Pharmaceutical Company Limited, Nanjing, P. R. China
- 6Centre for Computational Biology, Duke-NUS Medical School, Outram, Singapore
- 7Department of Medicine Huddinge, Unit for Gastroenterology and Nutrition, Karolinska Institute, Huddinge, Sweden
- 8Research Center for High Altitude Medicine, Laboratory for High Altitude Medicine of Qinghai Province, Qinghai University, Xining, P. R. China
- 9Department of Dermatology, First Affiliated Hospital, Nanjing Medical University, Nanjing, P. R. China. [email protected]
- 10State Key Laboratory of Pharmaceutical Biotechnology, State Key Laboratory of Analytical Chemistry for Life Science, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, P. R. China. [email protected]
- 11State Key Laboratory of Pharmaceutical Biotechnology, State Key Laboratory of Analytical Chemistry for Life Science, Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, P. R. China. [email protected]
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.
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BibTeX
@article{lian2026microbiotainduced,
title = {{Gut microbiota-induced perturbation in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasis}},
author = {Panpan Lian and Renwei Lu and Chaode Gu and Junaid Wazir and Wentong Wang and Yangyongyi Zong and Yun Xia and Jie Ni and Huimei Chen and Enrico G. Petretto and Eckardt Treuter and Rongrong Fan and Airong Yang and Zhonglan Su and Hongwei Wang and Zhiqiang Huang},
journal = {Nature Communications},
year = {2026},
month = may,
doi = {10.1038/s41467-026-72417-5},
url = {https://doi.org/10.1038/s41467-026-72417-5},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Gut microbiota-induced perturbation in bile acids alter keratinocyte lipid metabolism via FXR-NQO1 signaling in psoriasis
AU - Panpan Lian
AU - Renwei Lu
AU - Chaode Gu
AU - Junaid Wazir
AU - Wentong Wang
AU - Yangyongyi Zong
AU - Yun Xia
AU - Jie Ni
AU - Huimei Chen
AU - Enrico G. Petretto
AU - Eckardt Treuter
AU - Rongrong Fan
AU - Airong Yang
AU - Zhonglan Su
AU - Hongwei Wang
AU - Zhiqiang Huang
PY - 2026
DA - 2026/05/18
JO - Nature Communications
DO - 10.1038/s41467-026-72417-5
UR - https://doi.org/10.1038/s41467-026-72417-5
AB - 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.
SN - 2041-1723
ER -