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

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. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-023-01007-w.

The Mediterranean Diet as a Potential Solution to the Gut Microbiome Dysbiosis in Psoriasis Patients

“…14,16,17 From the mendelian randomization study, the genus Prevotella was found to possibly have a protective impact (OR .87 [95% CI: .76-1.00] whereas Eubacterium fissicatena conferred an increase risk for psoriasis (OR 1.22 [95% CI: 1.10-1.35]). 25 The Prevotella genus was found to be decreased in a psoriasis cohort in a study that took place in Israel. 18 In the same family as Prevotella , the genus Paraprevotella was found to be decreased in two studies.…”

“…They found that Bacteroidetes have a protective role in psoriasis (OR .81 [95% CI .67-.98]), further supporting the findings of low Bacteroidetes in psoriasis patients from previous studies. 25…”

“…They found that Bacteroidetes have a protective role in psoriasis (OR .81 [95% CI .67-.98]), further supporting the findings of low Bacteroidetes in psoriasis patients from previous studies. 25 The next level of taxonomy is the genera level. In terms of significant findings for Scher at al., Parabacteroides genus was reduced compared to healthy controls which was replicated in one other study.…”

Causal relationship between gut microbiota and prostate cancer contributes to the gut-prostate axis: insights from a Mendelian randomization study

“…Despite the absence of specific studies on the relationship between the E. fissicatena group and prostate cancer, Zang et al discovered a causal relationship between E. fissicatena and psoriasis. This finding suggests that gut microbes play a role in mediating the modulation of relevant immune responses [ 35 ].…”

Genetic insights into the gut microbiota and risk of facial skin aging: A Mendelian randomization study

“…Mendelian randomization (MR) reveals the relationship between various phenotypes and diseases by examining exposure‐related variables to assess causal relationships that may be associated with outcomes. To date, large‐scale Genome‐Wide Association Study(GWAS) of the GM has been applied to a variety of skin diseases, for example, psoriasis, 17 lichen planus, 18 and urticaria 19 . MR analysis can help researchers to determine the causal relationship between GM and these skin diseases, and to explore the potential impact of GM on skin diseases.…”