Background and aims: The causal relationship between gut microbiota and gout and hyperuricemia (HUA) has not been clarified. The objective of this research was to evaluate the potential causal effects of gut microbiota on HUA and gout using a two-sample Mendelian randomization (MR) approach.
Methods and results: Genetic instruments were selected using summary statistics from genome-wide association studies (GWASs) comprising a substantial number of individuals, including 18,473 participants for gut microbiome, 288,649 for serum urate (SU), and 763,813 for gout. Two-sample MR analyses were performed to determine the possible causal associations of gut microbial genera with the risk of HUA and gout using the inverse-variance weighted (IVW) method, and robustness of the results was confirmed by several sensitivity analyses. A reverse MR analysis was conducted on the bacterial taxa that were identified in forward MR analysis. Based on the results of MR analyses, Escherichia-Shigella (OR = 1.05; 95% CI, 1.01-1.08; P = 0.009) exhibited a positive association with SU levels, while Lachnospiraceae NC2004 group (OR = 0.95; 95% CI, 0.92-0.98; P = 0.001) and Family XIII AD3011 group (OR = 0.94; 95% CI, 0.90-0.99; P = 0.015) were associated with a reduced HUA risk. Moreover, Coprococcus 3 (OR = 1.17, 95% CI: 1.01-1.34, P = 0.031) was causally associated with a higher gout risk. In reverse MR analysis, no causal relationships were identified between these bacterial genera and HUA or gout.
Conclusion: This study provides evidence for a causal association between gut microbial genera and HUA or gout, and further investigations of the underlying mechanism are warranted.
Keywords: Gout; Gut microbial genera; Hyperuricemia; Mendelian randomization; Serum urate.
Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.