Causal relationship between gut and risk of sepsis: a two-sample Mendelian randomization and clinical retrospective study in the framework of predictive, preventive, and personalized medicine.

Objective: Gut microbiota is closely related to sepsis. Recent studies have suggested that could be associated with intestinal inflammation; however, the causal relationship between and sepsis remains uncertain. From the perspective of predictive, preventive, and personalized medicine (PPPM), exploring the causal relationship between gut and sepsis could provide opportunity for targeted prevention and personalized treatment.

Methods: The genome-wide association study (GWAS) summary-level data of ( = 7738) and sepsis were obtained from the Dutch Microbiome Project and the UK Biobank (sepsis, 1380 cases; 429,985 controls). MR analysis was conducted to estimate the associations between and sepsis risk. The 16S rRNA sequencing analysis was conducted to calculate the relative abundance of in sepsis patients to explore the relationship between relative abundance and the 28-day mortality.

Results: Genetic liability to f__ (OR, 1.91; CI, 1.35-2.71;  = 0.0003) was associated with a high risk of sepsis with inverse-variance weighted (IVW). The median relative abundance in non-survivors was significantly higher than in survivors (2.34% vs 0.17%,  < 0.001). Multivariate analysis confirmed that relative abundance (OR, 1.10; CI, 1.03-1.22;  = 0.027) was an independent factor of 28-day mortality in sepsis patients. ROC curve analysis indicated that relative abundance (AUC: 0.787, 95% CI: 0.671-0.902,  = 0.0003) could predict the prognosis of sepsis patients.

Conclusion: Our results revealed that was causally associated with sepsis and affected the prognosis of sepsis patients. These findings may provide insights to clinicians on developing improved sepsis PPPM strategies.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00340-6.