CD8 + T cells may mediate the effect of gut microbiota on psoriasis: evidence from two-step mendelian randomization...

Emerging research indicates that gut microbiota and the associated immune responses are crucial in the development of chronic inflammatory skin diseases. This investigation employs Mendelian Randomization (MR) and Bayesian weighting to elucidate the causal links between gut microbiota, immune cells, and psoriasis, with a specific emphasis on CD8 + T cells. We leveraged summary statistics from genome-wide association studies (GWAS) related to gut microbiota, immune cells, and psoriasis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs) to evaluate causal relationships through various MR methods, such as inverse variance weighted (IVW), MR Egger, weighted median, and simple mode. Additionally, Bayesian weighting was used to validate results and account for potential pleiotropy. The IVW analysis revealed significant associations between certain gut microbiota and psoriasis, notably identifying a protective link between Escherichia coli and psoriasis. Further MR analysis demonstrated that Escherichia coli had a causal relationship with CD8 + T cells. Increased levels of CD8 + T cells were associated with a higher risk of psoriasis. BWMR analysis confirmed these findings, showing that CD8 + T cells mediated 10.09% of the protective effect of Escherichia coli on psoriasis. This study underscores the significant role of Escherichia coli and CD8 + T cells in psoriasis, suggesting both protective and exacerbating effects. Understanding these microbiota-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.