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Background: To investigate the causal role of lipid in sepsis and determine the effect of lipid-lowering interventions on the disease. Methods: Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B and apolipoprotein A-I levels with risks for sepsis, and those of low-density lipoprotein cholesterol (HMGCR, PCSK9, NPC1L1), triglycerides (LPL, ANGPTL3, APOC3) and high-density lipoprotein cholesterol (CETP), apolipoprotein A-I (CETP), apolipoprotein B (HMGCR, PCSK9, NPC1L1, LPL, APOC3) with sepsis. Results: HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis, with an odds ratio value of 1.4 (95% confidence interval (CI): 1.06-1.84, P = 0.017) and 1.41 (95% CI: 1.01-1.98, P = 0.046). CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis, with an odds ratio of 0.87 (95% CI: 0.82-0.92, P < 0.01) respectively and 0.84 (95% CI: 0.78-0.9, P < 0.01). Sensitivity analysis showed that the results were robust. Conclusion: HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis. [ABSTRACT FROM AUTHOR]

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]