Mendelian randomization analysis of causal relationship between gut microbiota and gout
LI Yunhe
PANG Jing
GUO Dongmei
LI Chunpu
Abstract：Objective Mendelian randomization analysis was used to investigate the causal relationship between gut microbiota and gout.Methods Single-nucleotide polymorphism(SNP)data related to the gut microbiota were derived from genome-wide meta-analyses,including 18,340 participants of diverse ethnicities.As reported,all participating co-horts implemented standardized 16S rRNA processing pipelines,ultimately summarizing 211 taxonomic groups(131 gen-era,35 families,20 orders,16 classes,and 9 phyla).Gout-realted SNP data were obtained from the FinnGen consortium R8 release data,which included 7,461 gout cases and 221,323 controls.Using SNP as the instrumental variable,gut mi-crobiota as the exposure factor,and gout as the outcome.We chose three methods for MR:inverse variance weighted(IVW),weighted median and MR-Egger.The result of IVW was deemed as the primary result.Moreover,quantifying in-strumental variable heterogeneity was done using Cochran's Q statistics.Finally,reverse-direction MR analysis were per-formed to rule out the possibility of reverse associations.Results Totally 196 types of gut microbiota were included,and 2,248 relevant SNP sites were identified through standard screening.IVW analysis suggested that Bacteroidia class(OR=1.28,95%CI=1.06-1.56,P=0.012),Streptococcaceae family(OR=1.22,95%CI=1.00-1.48,P=0.045),Anaero-stipes genus(OR=1.27,95%CI=1.05-1.53,P=0.013),Ruminococcus2 genus(OR=1.16,95%CI=1.01-1.33,P=0.042),Streptococcus genus(OR=1.23,95%CI=1.01-1.50,P=0.038),Bacteroidales order(OR=1.28,95%CI=1.06-1.56,P=0.012)and Bacteroidetes phylum(OR=1.33,95%CI=1.08-1.64,P=0.007 3)were positively correlat-ed with the risk of gout,while Eubacteriumhalliigroup genus(OR=0.81,95%CI=0.68-0.96,P=0.015),Ruminococca-ceaeUCG010 genus(OR=0.78,95%CI=0.63-0.97,P=0.023),and Subdoligranulum genus(OR=0.83,95%CI=0.69-1.00,P=0.047)were negatively correlated with the risk of gout.Sensitivity analysis showed robust results,and no pleiot-ropy,heterogeneity,or reverse causality was observed.Conclusions There is a causal relationship between gut microbi-ota and the risk of gout.Bacteroidia class,Streptococcaceae family,Anaerostipes genus,Ruminococcus2 genus,Strepto-coccus genus,Bacteroidales order and Bacteroidetes phylum were risk factors for gout.Eubacteriumhalliigroup genus,Ru-minococcaceaeUCG010 genus,and Subdoligranulum genus were protective factors for gout.
Keywords：goutintestinal floracausalityMendelian randomizationgenome-wide association study
Publication Date：2025-06-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 37-41 )