Mendelian randomization study of causal link from gut microbiota to gout

Objective Mendelian randomization analysis was used to investigate causal relationships between gut microbiota and gout.Method For exposure data, we extracted genetic variants associated with 194 bacterial traits from MiBioGen consortium (n=18340) which conducted a meta-analysis of genome-wide association studies. For outcome data, summary data of gout was from the FinnGen consortium. We chosed three methods for MR: inverse variance weighted, weighted median and MR-Egger. The result of IVW was deemed as the primary result. Moreover, quantifying instrumental variable heterogeneity was done using Cochran's Q statistics. Finally, reverse-direction MR analysis were performed to rule out the possibility of reverse associations.Results Inverse variance weighted estimates suggested that Bacteroidia class (OR=1.28,95%CI=1.06-1.56,P=1.2×10-2), Streptococcaceae family (OR=1.22,95%CI=1.00-1.48,P=4.5×10-2), Anaerostipes genus (OR=1.27,95%CI=1.05-1.53,P=1.3×10-2), Ruminococcus2 genus (OR=1.16,95%CI=1.01-1.33,P=4.2×10-2), Streptococcus genus (OR=1.23,95%CI=1.01-1.50,P=3.8×10-2), Bacteroidales order (OR=1.28,95%CI=1.06-1.56,P=1.2×10-2) and Bacteroidetes phylum (OR=1.33,95%CI=1.08-1.64,P=7.3×10-3) were potentially associated with a higher risk gout, while Eubacteriumhalliigroup genus (OR=0.81,95%CI=0.68-0.96,P=1.5×10-2), RuminococcaceaeUCG010 genus (OR=0.78,95%CI=0.63-0.97,P=2.3×10-2), Subdoligranulum genus (OR=0.83,95%CI=0.69-1.00,P=4.7×10-2) were protective factors for gout.Conclusions There is a causal relationship between gut microbiota and the risk of gout. Bacteroidia class, Streptococcaceae family, Anaerostipes genus, Ruminococcus2 genus, Streptococcus genus, Bacteroidales order and Bacteroidetes phylum were potentially associated with a higher risk gout. Eubacteriumhalliigroup genus, RuminococcaceaeUCG010 genus, Subdoligranulum genus were protective factors for gout.