Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study

Chenyang Zang; Jie Liu; Manyun Mao; Wu Zhu; Wangqing Chen; Baojian Wei

doi:10.1007/s13555-023-01007-w

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study

Dermatol Ther (Heidelb). 2023 Oct;13(10):2331-2343. doi: 10.1007/s13555-023-01007-w. Epub 2023 Aug 31.

Authors

Chenyang Zang^{1

2

3

4

5}, Jie Liu⁵, Manyun Mao^{1

2

3

4}, Wu Zhu^{6

7

8

9}, Wangqing Chen^{10

11

12

13}, Baojian Wei¹⁴

Affiliations

¹ The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
² National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Furong Laboratory, Changsha, China.
³ Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, China.
⁴ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
⁵ Xiangya School of Medicine, Central South University, Changsha, China.
⁶ The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. zhuwu70@hotmail.com.
⁷ National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Furong Laboratory, Changsha, China. zhuwu70@hotmail.com.
⁸ Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, China. zhuwu70@hotmail.com.
⁹ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China. zhuwu70@hotmail.com.
¹⁰ The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. lanchen2008@163.com.
¹¹ National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Furong Laboratory, Changsha, China. lanchen2008@163.com.
¹² Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, China. lanchen2008@163.com.
¹³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China. lanchen2008@163.com.
¹⁴ School of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, China. bjwei@sdfmu.edu.cn.

Abstract

Introduction: Previous studies have proposed a possible gut-skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis.

Methods: With published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis.

Results: By primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR 0.81, P = 0.033) and Prevotella9 (OR 0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR 0.65, P = 0.03), Bacteroidales (OR 0.65, P = 0.03), and Ruminococcaceae UCG002 (OR 0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR 1.22, P = 0.033), Pasteurellaceae (OR 1.22, P = 0.033), Blautia (OR 1.46, P = 0.014), Methanobrevibacter (OR 1.27, P = 0.026), and Eubacterium fissicatena group (OR 1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E. fissicatena group is a possible risk factor for psoriasis (OR 1.22, P = 0.00018). After false discovery rate (FDR) correction, E. fissicatena group remains a risk factor for psoriasis (P_FDR = 0.03798).

Conclusion: We comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E. fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management.

Keywords: Causal analysis; Gut microbiota; Gut–skin axis; Mendelian randomization; Psoriasis.

Abstract

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