Causal effects of gut microbiota on 28-day mortality in patients with sepsis: a Mendelian randomization analysis

Sepsis, which is characterized by the failure of multiple organ, is the leading cause of death in intensive care units. Extensive research has emphasized a significant link between sepsis and the gut microbiota (GM). However, the causal relationship between these two factors, specifically the impact on 28-day mortality, remains unclear. We conducted a Mendelian randomization (MR) study utilizing genome-wide association study (GWAS) summary statistics. The primary analysis method used to establish the causal relationship was the inverse-variance weighted (IVW) method, along with four other MR methods. Furthermore, we assessed heterogeneity and horizontal pleiotropy using Cochran's Q test, MR-Egger intercept test, respectively. The IVW method showed that 7 GM, mainly including class Bacteroidia [odd ratio (OR) 1.565, 95% confidence interval (CI) 1.161-2.108, P = 0.003], genus Methanobrevibacter (OR 1.347, 95% CI 1.045-1.736, P = 0.022) and others were positively associated with 28-day sepsis mortality. Conversely, genetically predicted 4 GM, including class Lentisphaeria (OR 0.751, 95% CI 0.588-0.960, P = 0.022), genus Coprococcus2 (OR 0.537, 95% CI 0.315-0.917, P = 0.023), and others were negatively related to 28-day sepsis mortality. Heterogeneity and pleiotropy analyses also confirmed the robustness of our findings (all P > 0.05). Our study demonstrated a causal relationship between GM and 28-day mortality in sepsis using MR methods from a genetic perspective, wihich provides prospects for future microbiome-based therapeutics target in sepsis.