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

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

doi:10.1007/s13167-023-00340-6

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

EPMA J. 2023 Oct 12;14(4):697-711. doi: 10.1007/s13167-023-00340-6. eCollection 2023 Dec.

Authors

Yinghao Luo^{1

2}, Yang Zhou^{1

2}, Pengfei Huang^{1

2}, Qianqian Zhang^{1

2}, Feiyu Luan^{1

2}, Yahui Peng^{1

2}, Jieling Wei^{1

2}, Nana Li^{1

2}, Chunying Wang^{1

2}, Xibo Wang^{1

2}, Jiannan Zhang^{1

2}, Kaijiang Yu^{1

2}, Mingyan Zhao^{1

2}, Changsong Wang^{1

2}

Affiliations

¹ Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang China.
² Heilongjiang Provincial Key Laboratory of Critical Care Medicine, 23 Postal Street, Nangang District, Harbin, 150001 Heilongjiang China.

PMID: 38094582
PMCID: PMC10713913 (available on 2024-12-01)
DOI: 10.1007/s13167-023-00340-6

Abstract

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.

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

Keywords: Gut microbiota; Mendelian randomization; Predictive preventive personalized medicine; Prevotellaceae; Sepsis.

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