No Causal Association Between Gut Microbiota and Kawasaki Disease: A Two-Sample Mendelian Randomization Study

Background: Despite previous observational studies linking gut microbiota to Kawasaki disease (KD), these findings remain controversial. This study aimed to explore the association between gut microbiota and KD at a genetic level, using a two-sample Mendelian randomization (MR) analysis. Methods: A two-sample MR study utilized summary statistics of gut microbiota from the largest genome-wide association study meta-analysis by the MiBioGen consortium. The causal link between gut microbiota and KD was examined using inverse variance weighted, MR Egger, weighted median, simple mode, weighted mode, and MR-PRESSO methods. Reverse MR analysis was conducted on bacteria identified as causally linked to KD in the initial MR study. Cochran’s Q and Rucker’s Q statistics quantified the heterogeneity among instrumental variables. Results: Inverse variance weighted estimates suggested no genetic causal correlation with KD for the following taxa: genus Bifidobacterium(p = 0.774, OR 95% CI = 0.876 [0.355–2.163]), genus FamilyXIIIAD3011group(p = 0.945, OR 95% CI = 0.979 [0.539–1.780]), genus LachnospiraceaeUCG004(p = 0.987, OR 95%CI = 1.005 [0.542–1.863]), genus RuminococcaceaeNK4A214group (p = 0.453, OR 95%CI = 1.469 [0.538–4.009]), genus RuminococcaceaeUCG002 (p = 0.835, OR 95% CI = 1.092 [0.478–2.494]), genus LachnospiraceaeUCG001 (p = 0.996, OR 95%CI = 0.998 [0.482–2.066]), genus Bacteroides (p = 0.595, OR 95%CI = 0.831 [0.419–1.648]), genus Olsenella (p = 0.414, OR 95%CI = 1.312 [0.684–2.516]), genus Lactococcus (p = 0.870, OR 95%CI = 0.962 [0.600–1.541]), family Rhodospirillaceae (p = 0.995, OR 95%CI = 1.002 [0.550–1.827]), family FamilyXIII (p = 0.894, OR 95%CI = 1.093 [0.298–4.009]), family BacteroidalesS24 (p = 0.604, OR 95%CI = 0.849 [0.456–1.578]), family Ruminococcaceae (p = 0.524, OR 95%CI = 0.692 [0.223–2.148]), and class Bacilli (p = 0.905, OR 95%CI = 0.967 [0.561–1.667]). The reverse MR analysis revealed no significant causal effect of KD on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was observed. Conclusion: Our bidirectional causal inference analysis revealed no genetic causal relationship between gut microbiota and KD. Confounding factors might have influenced the observed association in observational studies. Further research requires more advanced MR analysis methods, and larger-scale GWAS datasets.