Causal effects of gut microbiota on sepsis: a two-sample Mendelian randomization study

Frontiers in Microbiology

Microbiology

Jie-Hai Chen¹  Ke-Xuan Liu¹  Yong-Qiang Deng²  Hao-Xuan Tang²  Yun-Feng Zhao²  Hang Lei²  Li-Ying Zeng²  Yu-Fei Wan² 

[1] Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China;

关键词: Mendelian randomization;    gut microbiota;    sepsis;    causal inference;    genetics;   

DOI  :  10.3389/fmicb.2023.1167416

 received in 2023-02-16, accepted in 2023-04-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundRecent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear.MethodsThe present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS (N = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10−5) and the genome-wide statistical significance threshold (5 × 10−8) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran’s Q test, and leave-one-out test, were carried out to assess the robustness of our findings.ResultsOur study suggested that increased abundance of Deltaproteobacteria, Desulfovibrionales, Catenibacterium, and Hungatella were negatively associated with sepsis risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group, and Terrisporobacter were positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy.ConclusionThis study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Zeng, Zhao, Tang, Lei, Wan, Deng and Liu.