关键词: COVID-19 Mendelian randomization gut microbiota inflammatory proteins meta

Mesh : Humans COVID-19 / genetics immunology Mendelian Randomization Analysis Gastrointestinal Microbiome / genetics SARS-CoV-2 / physiology Bayes Theorem Inflammation

来  源:   DOI:10.3389/fimmu.2024.1406291   PDF(Pubmed)

Abstract:
UNASSIGNED: The human gut microbiota has been identified as a potentially important factor influencing the development of COVID-19. It is believed that the disease primarily affects the organism through inflammatory pathways. With the aim of improving early diagnosis and targeted therapy, it is crucial to identify the specific gut microbiota associated with COVID-19 and to gain a deeper understanding of the underlying processes. The present study sought to investigate the potential causal relationship between the gut microbiota and COVID-19, and to determine the extent to which inflammatory proteins act as mediators in this relationship.
UNASSIGNED: Bidirectional mendelian randomization (MR) and Two-step mediated MR analyses were applied to examine causative associations among 196 gut microbiota, 91 inflammatory proteins and COVID-19. The main analytical method used in the MR was the random effects inverse variance weighted (IVW) method. This was complemented by the Bayesian weighted Mendelian randomization (BWMR) method, which was utilized to test the hypothesis of MR. In order for the results to be deemed reliable, statistical significance was required for both methods. Validation was then carried out using an external dataset, and further meta-analyses were conducted to authenticate that the association was reliable.
UNASSIGNED: Results of our research indicated that seven gut microbiota were actively associated to the COVID-19 risk. Five inflammatory proteins were associated with COVID-19 risk, of which three were positively and two were negatively identified with COVID-19. Further validation was carried out using sensitivity analyses. Mediated MR results revealed that CCL2 was a possible mediator of causality of family Bifidobacteriaceae and order Bifidobacteriales with COVID-19, mediating at a ratio of 12.73%.
UNASSIGNED: Suggesting a genetic causation between specific gut microbiota and COVID-19, our present research emphasizes the underlying mediating role of CCL2, an inflammatory factor, and contributes to a deeper understanding of the mechanism of action underlying COVID-19.
摘要:
人类肠道菌群已被确定为影响COVID-19发展的潜在重要因素。认为该疾病主要通过炎症途径影响生物体。为了提高早期诊断和靶向治疗,确定与COVID-19相关的特定肠道微生物群并更深入地了解其潜在过程至关重要。本研究试图调查肠道微生物群与COVID-19之间的潜在因果关系,并确定炎症蛋白在这种关系中充当介质的程度。
双向孟德尔随机化(MR)和两步介导的MR分析用于检查196个肠道微生物群之间的因果关系,91种炎症蛋白和COVID-19。MR中使用的主要分析方法是随机效应逆方差加权(IVW)方法。贝叶斯加权孟德尔随机化(BWMR)方法补充了这一点,用于检验MR的假设。为了使结果被认为是可靠的,两种方法都需要统计学意义.然后使用外部数据集进行验证,我们进行了进一步的荟萃分析,以验证该关联是可靠的.
我们的研究结果表明,七种肠道微生物群与COVID-19风险积极相关。五种炎症蛋白与COVID-19风险相关,其中3人在COVID-19中呈阳性,2人呈阴性。使用敏感性分析进行进一步验证。介导的MR结果显示,CCL2可能是双歧杆菌科和双歧杆菌科与COVID-19因果关系的介质,介导率为12.73%。
提示特定肠道微生物群与COVID-19之间存在遗传因果关系,我们目前的研究强调了炎症因子CCL2的潜在介导作用,并有助于更深入地了解COVID-19的作用机制。
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