肠道微生物群、炎症蛋白与 COVID-19：一项孟德尔随机化研究。

Gut microbiota, inflammatory proteins and COVID-19: a Mendelian randomisation study.

机构信息

Department of Clinical Laboratory, Nanchong Central Hospital (Nanchong Hospital of Beijing Anzhen Hospital, Capital Medical University), The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan, China.

Medical Department, Nanchong Guoning Mental Health Hospital, Nanchong, Sichuan, China.

出版信息

Front Immunol. 2024 May 13;15:1406291. doi: 10.3389/fimmu.2024.1406291. eCollection 2024.

DOI:10.3389/fimmu.2024.1406291

PMID:38803488

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11128586/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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%.

CONCLUSION

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

背景

人类肠道微生物群已被确定为影响 COVID-19 发展的一个潜在重要因素。据信，该疾病主要通过炎症途径影响机体。为了提高早期诊断和靶向治疗的效果，识别与 COVID-19 相关的特定肠道微生物群并深入了解潜在的作用机制至关重要。本研究旨在探讨肠道微生物群与 COVID-19 之间的潜在因果关系，并确定炎症蛋白在这种关系中作为中介的程度。

方法

采用双向孟德尔随机化（MR）和两步中介 MR 分析方法，研究了 196 种肠道微生物群、91 种炎症蛋白和 COVID-19 之间的因果关系。MR 的主要分析方法是随机效应逆方差加权（IVW）方法。此外，还采用了贝叶斯加权孟德尔随机化（BWMR）方法来检验 MR 假设。两种方法均需具有统计学意义，结果才被认为可靠。然后使用外部数据集进行验证，并进行进一步的荟萃分析以验证该关联的可靠性。

结果

研究结果表明，有七种肠道微生物群与 COVID-19 风险呈正相关。五种炎症蛋白与 COVID-19 风险相关，其中三种与 COVID-19 呈正相关，两种呈负相关。进一步的验证通过敏感性分析进行。中介 MR 结果表明，CCL2 可能是科双歧杆菌科和目双歧杆菌属与 COVID-19 因果关系的中介，介导比例为 12.73%。