Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation

Abstract

Background: It is unclear what the causal relationship is between the gut microbiota and sepsis. Therefore, we employed Mendelian randomization (MR) to determine whether a causal link exists between the two.

Methods: This study used publicly available genome-wide association studies (GWAS) summary data of gut microbiota, sepsis, sepsis (critical care), and sepsis (28-day death in critical care) to perform a two-sample MR analysis. To ensure the robustness of the results, we also conducted a sensitivity analysis.

Results: For sepsis susceptibility, inverse variance weighted (IVW) estimates revealed that Victivallales (OR = 0.86, 95% CI, 0.78-0.94, p = 0.0017) was protective against sepsis, while Lentisphaerae (OR = 0.89, 95% CI, 0.80-0.99), Gammaproteobacteria (OR = 1.37, 95% CI, 1.08-1.73), Clostridiaceae1 (OR = 1.21, 95% CI, 1.04-1.40), RuminococcaceaeUCG011 (OR = 1.10, 95% CI, 1.01-1.20), Dialister (OR = 0.85, 95% CI, 0.74-0.97), and Coprococcus2 (OR = 0.81, 95% CI, 0.69-0.94) presented a suggestive association with the development of sepsis (all p < 0.05). For sepsis (critical care), IVW estimates indicated that Lentisphaerae (OR = 0.70, 95% CI, 0.53-0.93), Victivallales (OR = 0.67, 95% CI, 0.50-0.91), Anaerostipes (OR = 0.49, 95% CI, 0.31-0.76), LachnospiraceaeUCG004 (OR = 0.51, 95% CI, 0.34-0.77), and Coprococcus1 (OR = 0.66, 95% CI, 0.44-0.99) showed a suggestive negative correlation with sepsis (critical care) (all p < 0.05). For sepsis (28-day death in critical care), IVW estimates suggested that four bacterial taxa had a normally significant negative correlation with the risk of sepsis-related death, including Victivallales (OR = 0.54, 95% CI, 0.30-0.95), Coprococcus2 (OR = 0.34, 95% CI, 0.14-0.83), Ruminiclostridium6 (OR = 0.43, 95% CI, 0.22-0.83), and Coprococcus1 (OR = 0.45, 95% CI, 0.21-0.97), while two bacterial taxa were normally significantly positively linked to the risk of sepsis-related death, namely, Mollicutes (OR = 2.03, 95% CI, 1.01-4.08) and Bacteroidales (OR = 2.65, 95% CI, 1.18-5.96) (all p < 0.05). The robustness of the above correlations was verified by additional sensitivity analyses.

Conclusion: This MR research found that several gut microbiota taxa were causally linked to the risk of sepsis, sepsis in critical care, and sepsis-related 28-day mortality in critical care.

Keywords: Mendelian randomization; causality; gut microbiota; sepsis; sepsis-related death.