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

作者：Luo, Yinghao; Zhou, Yang; Huang, Pengfei; Zhang, Qianqian; Luan, Feiyu; Peng, Yahui; Wei, Jieling; Li, Nana; Wang, Chunying; Wang, Xibo; Zhang, Jiannan; Yu, Kaijiang^*; Zhao, Mingyan^*; Wang, Changsong^*

来源：The EPMA Journal, 2023, 14(4): 697-711.

DOI：10.1007/s13167-023-00340-6

• Prevotellaceae
• Prevotellaceae
• Sepsis
• Mendelian randomization
• Gut microbiota
• Predictive preventive personalized medicine

Objective Gut microbiota is closely related to sepsis. Recent studies have suggested that Prevotellaceae could be associated with intestinal inflammation; however, the causal relationship between Prevotellaceae and sepsis remains uncertain. From the perspective of predictive, preventive, and personalized medicine (PPPM), exploring the causal relationship between gut Prevotellaceae and sepsis could provide opportunity for targeted prevention and personalized treatment.Methods The genome-wide association study (GWAS) summary-level data of Prevotellaceae (N = 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 Prevotellaceae and sepsis risk. The 16S rRNA sequencing analysis was conducted to calculate the relative abundance of Prevotellaceae in sepsis patients to explore the relationship between Prevotellaceae relative abundance and the 28-day mortality.Results Genetic liability to f__Prevotellaceae (OR, 1.91; CI, 1.35-2.71; p = 0.0003) was associated with a high risk of sepsis with inverse-variance weighted (IVW). The median Prevotellaceae relative abundance in non-survivors was significantly higher than in survivors (2.34% vs 0.17%, p < 0.001). Multivariate analysis confirmed that Prevotellaceae relative abundance (OR, 1.10; CI, 1.03-1.22; p = 0.027) was an independent factor of 28-day mortality in sepsis patients. ROC curve analysis indicated that Prevotellaceae relative abundance (AUC: 0.787, 95% CI: 0.671-0.902, p = 0.0003) could predict the prognosis of sepsis patients.Conclusion Our results revealed that Prevotellaceae 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.

• 单位
  1; 哈尔滨医科大学