Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Front Immunol. 2023 Aug 16;14:1211612. doi: 10.3389/fimmu.2023.1211612. eCollection 2023.
COVID-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.
Based 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.
MR 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 and with severe COVID-19, respectively. and could mediate the association of myo-inositol and N-acetylalanine, respectively. In addition, abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95).
Our 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.
COVID-19 可能会在某些感染患者中引发严重的呼吸道症状，尤其是在免疫功能紊乱的患者中。肠道微生物组和血浆代谢组在人体中充当重要的免疫调节剂，并可能有助于影响 COVID-19 进展的免疫反应。然而，特定肠道细菌、代谢物与严重 COVID-19 之间的因果关系尚不清楚。
基于两样本孟德尔随机化（MR）框架，评估了 131 种肠道分类群和 452 种血浆代谢物对严重 COVID-19 的因果效应。与肠道分类群丰度和血浆代谢物浓度强烈相关的单核苷酸多态性（SNP）被用作工具变量，以推断它们是否为严重 COVID-19 的因果因素。此外，进行了中介分析以发现分类群和代谢物之间的潜在关联，并进一步进行了共定位分析以验证因果关系。
MR 分析确定了 13 种分类群和 53 种代谢物，它们作为因果因素与严重 COVID-19 显著相关。中介分析揭示了 11 种中介关系。肌醇、2-硬脂酰甘油磷酸胆碱和α-谷氨酰酪氨酸分别可能是 和 与严重 COVID-19 相关的潜在因素。 和 分别可以介导肌醇和 N-乙酰丙氨酸的关联。此外， 丰度与严重 COVID-19 （PP.H4 = 0.77）和通透性相关蛋白 RASIP1 的结肠表达（PP.H4 = 0.95）共定位。
本研究强调了肠道微生物组、血浆代谢组与严重 COVID-19 之间的潜在因果关系，这些关系可能成为风险分层和预后的临床生物标志物，并有助于严重 COVID-19 发病机制的研究。
