Clinical rheumatology · 2025
Exploration of the mechanism of intestinal flora-mediated immune modulation in the pathogenesis of gout.
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Zhou Zeyu, Wang Siming, Liu Zenghui, Xue Qian, Wu Aoni, Sun Qiyu
Аннотация
INTRODUCTION: Although the role of immune cells in the pathogenesis of gout has been extensively studied, their interactions with the gut microbiota and the potential mediating effects in disease progression remain insufficiently characterized.
METHOD: This study used pooled data from genome-wide association studies (GWAS) to analyze associations among 731 immune cell phenotypes, 473 gut microbiota traits, and gout. A two-step mediation analysis identified microbiota potentially mediating the immune-gout relationship. Causal inference was primarily conducted using inverse-variance weighting (IVW), with MR-Egger, simple mode, weighted median, and weighted mode methods used to ensure robustness. Sensitivity analyses further confirmed the reliability of the findings.
RESULTS: Eight immune cell phenotypes were significantly linked to gout-five protective and three risk-related. Twenty gut microbial taxa were also associated, including seven protective and thirteen risk-related. Mediation analysis identified five microbial taxa (three genera, two species) mediating immune cell effects on gout. For example, higher TD CD8br %CD8br cells reduced gout risk by lowering Microvirga abundance (β = - 0.0315, P = 0.045), mediating 26.5%. In contrast, increased CD127 expression on CD28.
CONCLUSIONS: This study reveals a potential causal link between immune cells and gut microbiota in gout and identifies key microbial taxa involved. The findings deepen our understanding of gout pathogenesis and provide a basis for new therapeutic approaches. Key Points • Employed the authoritative FinnGen R12 disease database. • Utilized the latest gut microbiota GWAS data covering 473 microbial features. • Proposed a novel "immune cells-gut microbiota-gout" causal pathway. • Integrated multi-omics approaches for systematic mediation analysis.
METHOD: This study used pooled data from genome-wide association studies (GWAS) to analyze associations among 731 immune cell phenotypes, 473 gut microbiota traits, and gout. A two-step mediation analysis identified microbiota potentially mediating the immune-gout relationship. Causal inference was primarily conducted using inverse-variance weighting (IVW), with MR-Egger, simple mode, weighted median, and weighted mode methods used to ensure robustness. Sensitivity analyses further confirmed the reliability of the findings.
RESULTS: Eight immune cell phenotypes were significantly linked to gout-five protective and three risk-related. Twenty gut microbial taxa were also associated, including seven protective and thirteen risk-related. Mediation analysis identified five microbial taxa (three genera, two species) mediating immune cell effects on gout. For example, higher TD CD8br %CD8br cells reduced gout risk by lowering Microvirga abundance (β = - 0.0315, P = 0.045), mediating 26.5%. In contrast, increased CD127 expression on CD28.
CONCLUSIONS: This study reveals a potential causal link between immune cells and gut microbiota in gout and identifies key microbial taxa involved. The findings deepen our understanding of gout pathogenesis and provide a basis for new therapeutic approaches. Key Points • Employed the authoritative FinnGen R12 disease database. • Utilized the latest gut microbiota GWAS data covering 473 microbial features. • Proposed a novel "immune cells-gut microbiota-gout" causal pathway. • Integrated multi-omics approaches for systematic mediation analysis.