Investigating the gut microbiota's influence on psoriasis and psoriatic arthritis risk: a Mendelian randomization analysis.

Abstract

Numerous investigations have revealed the interplay between gut microbiota (GM) and psoriasis (Ps) and psoriatic arthritis (PsA). However, the causal relationship between them remains unknown. We curated a collection of genetic variants (P<1×10-5) associated with GM (n=18340) derived from the MiBioGen study. To explore the intricate relationship between GM and Ps as well as PsA, we harnessed the comprehensive resources of the FinnGen database, encompassing a vast cohort of individuals, including 4510 Ps cases and 212242 controls and 1637 PsA cases and 212242 controls. Mendelian randomization (MR) was used, including an inverse variance weighting method, followed by a sensitivity analysis to verify the robustness of the results. For Ps, some bacterial taxa, including Lactococcus, Ruminiclostridium 5, and Eubacterium fissicatena, were identified as risk factors; but Odoribacter demonstrated a protective effect against Ps. In the case of PsA, Lactococcus, Verrucomicrobiales, Akkermansia, Coprococcus 1, and Verrucomicrobiaceae were identified as risk factors; Odoribacter and Rikenellaceae exhibited a protective effect against the development of PsA. Our study establishes a causal link between the GM and Ps and PsA. These findings provide insights into the underlying mechanisms and suggest potential therapeutic targets.