School of Microbiology, University College Cork, Cork, Ireland.
APC Microbiome Ireland, University College Cork, Cork, Ireland.
Gut Microbes. 2023 Jan-Dec;15(1):2242615. doi: 10.1080/19490976.2023.2242615.
Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we performed a meta-analysis of eight shotgun metagenomic studies of COVID-19 patients (comprising 1,023 stool samples) and 23 > 16S rRNA gene amplicon sequencing (16S) cohorts (2,415 total stool samples). We found that disease severity (as defined by the WHO clinical progression scale) was associated with taxonomic and functional microbiome differences. This alteration in gut microbiome configuration peaks at days 7-30 post diagnosis, after which the gut microbiome returns to a configuration that becomes more similar to that of healthy controls over time. Furthermore, we identified a core set of species that were consistently associated with disease severity across shotgun metagenomic and 16S cohorts, and whose abundance can accurately predict disease severity category of SARS-CoV-2 infected subjects, with abundance predicting population-level mortality rate of COVID-19. Additionally, we used relational diet-microbiome databases constructed from cohort studies to predict microbiota-targeted diet patterns that would modulate gut microbiota composition toward that of healthy controls. Finally, we demonstrated the association of disease severity with the composition of intestinal archaeal, fungal, viral, and parasitic communities. Collectively, this study has identified robust COVID-19 microbiome biomarkers, established accurate predictive models as a basis for clinical prognostic tests for disease severity, and proposed biomarker-targeted diets for managing COVID-19 infection.
虽然许多最近的研究都检查了肠道微生物组与 COVID-19 患者个体队列疾病严重程度之间的关联,但他们报告的生物标志物在国际队列中的稳健性仍然存在疑问。在这里,我们对八项 COVID-19 患者的宏基因组研究(包括 1023 个粪便样本)和 23 个> 16S rRNA 基因扩增子测序(16S)队列(总共 2415 个粪便样本)进行了荟萃分析。我们发现疾病严重程度(由世界卫生组织临床进展量表定义)与分类和功能微生物组差异相关。这种肠道微生物组配置的改变在诊断后 7-30 天达到峰值,此后肠道微生物组随着时间的推移恢复到与健康对照组更相似的配置。此外,我们确定了一组与宏基因组和 16S 队列中疾病严重程度始终相关的核心物种,其丰度可以准确预测 SARS-CoV-2 感染受试者的疾病严重程度类别,其丰度预测 COVID-19 的人群死亡率。此外,我们使用从队列研究构建的关系饮食微生物组数据库来预测靶向微生物组的饮食模式,使肠道微生物组组成朝着健康对照组的方向改变。最后,我们证明了疾病严重程度与肠道古菌、真菌、病毒和寄生虫群落组成的关联。总的来说,这项研究确定了稳健的 COVID-19 微生物组生物标志物,建立了准确的预测模型作为疾病严重程度临床预后测试的基础,并提出了针对生物标志物的饮食来管理 COVID-19 感染。
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