Causal associations of gut microbiota and metabolites on sepsis: a two-sample Mendelian randomization study

Frontiers in Immunology

Immunology

Jian Zhao¹  Yi Zhao¹  Yugang Zhuang¹  Di Hao¹  Hu Peng¹  Shuqin Zhou¹  Yuanzhuo Chen¹  Xin Pan² 

[1] Department of Emergency, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China;Department of Gerontology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China;

关键词: sepsis;    gut microbiota;    gut metabolites;    Mendelian randomization;    causal associations;   

DOI  :  10.3389/fimmu.2023.1190230

 received in 2023-03-20, accepted in 2023-08-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundSepsis stands as a dire medical condition, arising when the body’s immune response to infection spirals into overdrive, paving the way for potential organ damage and potential mortality. With intestinal flora’s known impact on sepsis but a dearth of comprehensive data, our study embarked on a two-sample Mendelian randomization analysis to probe the causal link between gut microbiota and their metabolites with severe sepsis patients who succumbed within a 28-day span.MethodsLeveraging data from Genome-wide association study (GWAS) and combining it with data from 2,076 European descendants in the Framingham Heart Study, single-nucleotide polymorphisms (SNPs) were employed as Instrumental Variables (IVs) to discern gene loci affiliated with metabolites. GWAS summary statistics for sepsis were extracted from the UK Biobank consortium.ResultsIn this extensive exploration, 93 distinct genome-wide significant SNPs correlated with gut microbial metabolites and specific bacterial traits were identified for IVs construction. Notably, a substantial link between Coprococcus2 and both the incidence (OR of 0.80, 95% CI: 0.68-0.94, P=0.007) and the 28-day mortality rate (OR 0.48, 95% CI: 0.27-0.85, P=0.013) of sepsis was observed. The metabolite α-hydroxybutyrate displayed a marked association with sepsis onset (OR=1.08, 95% CI: 1.02-1.15, P=0.006) and its 28-day mortality rate (OR=1.17, 95% CI: 1.01-1.36, P=0.029).ConclusionThis research unveils the intricate interplay between the gut microbial consortium, especially the genus Coprococcus, and the metabolite α-hydroxybutyrate in the milieu of sepsis. The findings illuminate the pivotal role of intestinal microbiota and their metabolites in sepsis’ pathogenesis, offering fresh insights for future research and hinting at novel strategies for sepsis’ diagnosis, therapeutic interventions, and prognostic assessments.

【 授权许可】

Unknown   
Copyright © 2023 Zhao, Pan, Hao, Zhao, Chen, Zhou, Peng and Zhuang