The Causality of Gut Microbiota on Onset and Progression of Sepsis: a Bi-directional Mendelian Randomization Analysis

Background: Several observational studies have proposed a potential link between gut microbiota and the onset and progression of sepsis. Nevertheless, the causality of gut microbiota and sepsis remains debatable and warrants more comprehensive exploration.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis to test the causality between gut microbiota and the onset and progression of sepsis. The genome-wide association study (GWAS) summary statistics for 196 bacterial traits were extracted from the MiBioGen consortium, whereas the GWAS summary statistics for sepsis and sepsis-related outcomes came from the UK Biobank. The inverse-variance weighted (IVW) approach was the primary method used to examine the causal association. To complement the IVW method, we utilized four additional MR methods. We performed a series of sensitivity analyses to examine the robustness of the causal estimates.

Results: We assessed the causality of 196 bacterial traits on sepsis and sepsis-related outcomes. Genus [odds ratio (OR) 0.81, 95% confidence interval (CI) (0.69-0.94), = 0.007] and genus (OR 0.85, 95% CI 0.74-0.97, = 0.016) had a protective effect on sepsis, whereas genus (OR 1.10, 95% CI 1.01-1.20, = 0.024) increased the risk of sepsis. When it came to sepsis requiring critical care, genus (OR 0.49, 95% CI 0.31-0.76, = 0.002), genus (OR 0.65, 95% CI 0.43-1.00, = 0.049), and genus (OR 0.51, 95% CI 0.34-0.77, = 0.001) emerged as protective factors. Concerning 28-day mortality of sepsis, genus (OR 0.67, 95% CI 0.48-0.94, = 0.020), genus (OR 0.48, 95% CI 0.27-0.86, = 0.013), genus (OR 0.70, 95% CI 0.52-0.95, = 0.023), and genus (OR 0.82, 95% CI 0.68-0.99, = 0.042) presented a protective effect, whereas genus (OR 1.53, 95% CI 1.00-2.35, = 0.049), genus (OR 1.25, 95% CI 1.04-1.50, = 0.019), and genus (OR 1.43, 95% CI 1.02-2.02, = 0.040) presented a harmful effect. Furthermore, genus (OR 0.42, 95% CI 0.19-0.92, = 0.031), genus (OR 0.34, 95% CI 0.14-0.83, = 0.018), and genus (OR 0.43, 95% CI 0.22-0.83, = 0.012) were associated with a lower 28-day mortality of sepsis requiring critical care.

Conclusion: This MR analysis unveiled a causality between the 21 bacterial traits and sepsis and sepsis-related outcomes. Our findings may help the development of novel microbiota-based therapeutics to decrease the morbidity and mortality of sepsis.