Mitochondrial Function, Gut Microbiota, and Gout Risk Among Individuals of European Descent: A Mendelian Randomization Study of a Mediated Relationship.

Abstract

Purpose: Gout, a common form of arthritis, is characterised by recurrent episodes of severe inflammation owing to the accumulation of monosodium urate crystals in the joints and tissues, resulting from elevated serum uric acid levels. While the roles of gut microbiota and mitochondria in gout have been studied, their causal interactions remain unclear. The purpose of this study is to investigate the interplay between gut microbiota and mitochondrial biological function in the pathogenesis of gout.

Methods: This study utilized Mendelian randomization to explore causal links between mitochondrial biological function, gut microbiota, and gout, by leveraging data from genome-wide association studies. Bidirectional causal effects of mitochondrial biological functions on gout and serum uric acid levels were analysed; moreover, the causal effects of gut microbiota on gout and uric acid levels were evaluated through mediation analysis of the gut microbiota in the pathway linking mitochondrial biological function with gout.

Results: A causal relationship was found between mitochondrial biological function and gout mediated by gut microbiota. The NAD-dependent protein deacylase sirtuin-5 mediated 18.24% of the total effect on the adverse effects of gout by reducing creatinine degradation I. Calcium uptake protein 3 had a substantial impact on mitigating the negative effects of serum uric acid by decreasing the abundance of the order Burkholderiales and class Betaproteobacteria, which accounted for 16.52% and 15.83%, respectively, of the overall effect.

Conclusion: This analysis elucidated the complex relationships between mitochondrial biological function, gut microbiota, and gout, providing novel perspectives for gout prevention and treatment. Further investigations will enhance our understanding of the interactions between these biological processes and guide future intervention strategies.