Assessing causal relationships between gut microbiota and psoriasis: evidence from two sample Mendelian randomization analysis

Abstract

Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive. In this exploration, we adopted a Mendelian randomization (MR) strategy to probe the prospective causal interplay between the gut's microbial landscape and the predisposition to psoriasis. Genetic markers acting as instrumental variables for gut microbiota were extrapolated from a genome-wide association study (GWAS) encompassing 18,340 individuals. A separate GWAS yielded summary data for psoriasis, which covered 337,159 patients and 433,201 control subjects. The primary analysis hinged on inverse variance weighting (IVW). Additional methods like the weighted median approach and MR-Egger regression were employed to validate the integrity of our findings. Intriguing correlations emerged between psoriasis risk and eight specific bacterial traits. To illustrate: Mollicutes presented an odds ratio (OR) of 1.003 with a 95% confidence interval (CI) spanning 1.001-1.005 (p = 0.016), while the family. Victivallaceae revealed an OR of 0.998 with CI values between 0.997 and 0.999 (p = 0.023). Eubacterium (coprostanoligenes group) revealed an OR of 0.997 with CI values between 0.994 and 0.999 (p = 0.027). Eubacterium (fissicatena group) revealed an OR of 0.997 with CI values between 0.996 and 0.999 (p = 0.005). Holdemania revealed an OR of 1.001 with CI values 1-1.003 (p = 0.034). Lachnospiraceae (NK4A136 group) revealed an OR of 0.997 with CI values between 0.995 and 0.999 (p = 0.046). Lactococcus revealed an OR of 0.998 with CI values between 0.996 and 0.999 (p = 0.008). Tenericutes revealed an OR of 1.003 with CI values between 1.001 and 1.006 (p = 0.016). Sensitivity analysis for these bacterial features yielded congruent outcomes, reinforcing statistically significant ties between the eight bacterial entities and psoriasis. This comprehensive probe underscores emerging evidence pointing towards a plausible causal nexus between diverse gut microbiota and the onset of psoriasis. It beckons further research to unravel the intricacies of how the gut's microbial constituents might sway psoriasis's pathogenesis.

Keywords: GWAS; Genetics; Gut microbiota; Mendelian randomization; Psoriasis.

Figure 1

Study design of the MR analysis on the associations of gut microbiota and psoriasis. GWAS Genome Wide Association Studies, MR Mendelian randomization, SNP single nucleotide polymorphism.

Figure 2

Forest plot of the associations between genetically determined 8 bacterial traits with the risk of psoriasis. The results is displayed in the form of odds ratio (OR) accompanied by their 95% confidence interval (CI). An odds ratio below 1 indicates a reduction in the risk of urolithiasis, while one above 1 indicates an increased likelihood of contributing to the development of the disease. SNP single nucleotide polymorphism.

Figure 3

Scatter plots for the causal association between gut microbiota and psoriasis. The scatter plot shows that Mollicutes (A), Holdemania (E), Tenericutes (H) are positively correlated with the risk of psoriasis, while genus Victiallaceae (B), Eubacterium (coprostanoligenes group) (C), Eubacterium (fissicatena group) (D), Lachnospiraceae (NK4A136 group) (F) and Lactococcus (G) are negatively correlated with the risk of psoriasis. SNP single nucleotide polymorphism, MR Mendelian randomization.

Figure 4

Leave-one-out plots show that the causal relationship between Mollicutes (A), genus Victiallaceae (B), Eubacterium (coprostanoligenes group) (C), Eubacterium (fissicatena group) (D), Holdemania (E), Lachnospiraceae (NK4A136 group) (F), Lactococcus (G) and Tenericutes (H) was not driven by any single SNP. SNP single nucleotide polymorphism, MR Mendelian randomization.

Figure 5

Funnel plot to assess heterogeneity. The blue line represents the inverse‐variance weighted estimate, and the dark blue line represents the Mendelian randomization‐Egger estimate.