Gout drives metabolic dysfunction-associated steatotic liver disease through gut microbiota and inflammatory mediators

Abstract

Abstract This study explores the relationship between gout and metabolic dysfunction-associated steatotic liver disease (MASLD), two metabolic conditions linked to worsening health outcomes. While hyperuricemia’s association with MASLD is established, the specific connection between gout and MASLD remains less explored. Using data from the UK Biobank, the study employs COX proportional hazard models, multi-state survival analysis, and Mendelian randomization to assess the independent and mutual risks of gout and MASLD. Findings indicate a mutual risk increase: male gout patients, those younger than 60, and those with high BMI are particularly susceptible to MASLD, while female MASLD patients are at heightened risk for gout. Shared risk factors for both conditions include high BMI, hypertension, diabetes, and hyperuricemia. The study further identifies a bidirectional causal link, with gout leading to MASLD, mediated by gut microbiota Ruminococcaceae and proteins like IL-2 and GDF11, implicating specific metabolic pathways. The findings highlight a clinical and mechanistic correlation, emphasizing the need for targeted interventions to address these overlapping metabolic pathways in future treatments.

Keywords

• Gout
• MASLD
• Hyperuricemia
• Multi-state survival model
• Mendelian randomization