Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19

Frontiers in Immunology

Immunology

Xi Li¹  Han-Xue Huang¹  Yun-Dan Qu¹  Pan Xie¹  Si Zhao¹  Wei Zhang¹  Xin-He Cai¹  Jian-Quan Luo²  Han Yan²  Longbo Zhang³ 

[1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China;Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China;Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China;Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;Departments of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, Hunan, China;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China;Department of Neurosurgery, Yale School of Medicine, New Haven, CT, United States;

关键词: COVID-19;    gut microbiome;    plasma metabolites;    Mendelian randomization analysis;    mediation analysis;   

DOI  :  10.3389/fimmu.2023.1211612

 received in 2023-04-25, accepted in 2023-07-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundCOVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators in the human body and could contribute to the immune responses impacting the progression of COVID-19. However, the causal relationship between specific intestinal bacteria, metabolites and severe COVID-19 remains not clear.MethodsBased on two-sample Mendelian randomization (MR) framework, the causal effects of 131 intestinal taxa and 452 plasma metabolites on severe COVID-19 were evaluated. Single nucleotide polymorphisms (SNPs) strongly associated with the abundance of intestinal taxa and the concentration of plasma metabolites had been utilized as the instrument variables to infer whether they were causal factors of severe COVID-19. In addition, mediation analysis was conducted to find the potential association between the taxon and metabolite, and further colocalization analysis had been performed to validate the causal relationships.ResultsMR analysis identified 13 taxa and 53 metabolites, which were significantly associated with severe COVID-19 as causal factors. Mediation analysis revealed 11 mediated relationships. Myo-inositol, 2-stearoylglycerophosphocholine, and alpha-glutamyltyrosine, potentially contributed to the association of Howardella and Ruminiclostridium 6 with severe COVID-19, respectively. Butyrivibrio and Ruminococcus gnavus could mediate the association of myo-inositol and N-acetylalanine, respectively. In addition, Ruminococcus torques abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95).ConclusionsOur study highlights the potential causal relationships between gut microbiome, plasma metabolome and severe COVID-19, which potentially serve as clinical biomarkers for risk stratification and prognostication and benefit the mechanism mechanistic investigation of severe COVID-19.

【 授权许可】

Unknown   
Copyright © 2023 Yan, Zhao, Huang, Xie, Cai, Qu, Zhang, Luo, Zhang and Li