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Background: This study utilizes the two-sample Mendelian randomization method to examine the correlations between 196 variants of gut microbiota and sepsis. Methods: This study leveraged summary statistics data from the genome-wide association studies on gut microbiota and sepsis, obtained from MiBioGen (n = 18340) and the UK Biobank (n = 462918). Following pre-determined P-value and clumping thresholds, independently significant SNPs associated with the abundance of 196 gut microbiota were selected as instrumental variables. The primary methodology for the Mendelian randomization study involved the inverse-variance weighting method, with results being assessed based on the odds ratio and a 95% confidence interval. To assure the solidity of our findings, we executed an array of sensitivity analyses, encompassing the Mendelian randomization-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier test, Cochran's Q test, and the leave-one-out test. Results: An elevated presence of Bifidobacterium may diminish sepsis risk (odds ratio = 0.79; 95% confidence interval 0.72-0.86; P = 5.19e-07). No signs of heterogeneity or pleiotropy were exhibited in the sensitivity analysis. Conclusion: Bifidobacterium may be instrumental in reducing sepsis risk. [ABSTRACT FROM AUTHOR]