宏基因组分析揭示 COVID-19 患者口咽微生物群的改变。
Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19.
机构信息
Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin, China.
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
出版信息
Signal Transduct Target Ther. 2021 May 13;6(1):191. doi: 10.1038/s41392-021-00614-3.
COVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil-lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.
新型冠状病毒肺炎仍然是一个严重的全球新兴健康问题,人们对口咽共生微生物在感染易感性和严重程度中的作用知之甚少。在这里,我们通过对 31 例新型冠状病毒肺炎患者、29 例乙型流感患者和 28 例健康对照者的口咽拭子标本进行 shotgun 宏基因组测序分析,揭示了新型冠状病毒肺炎患者口咽微生物群的特征。我们的结果表明,新型冠状病毒肺炎患者的口咽微生物群组成明显不同,特征是机会性病原体如韦荣球菌属和巨球形菌属的富集和普氏菌属、罗氏菌属和链球菌属的消耗。基于口咽微生物组的相对丰度,我们构建了一个微生物分类器,以区分新型冠状病毒肺炎患者与流感患者和健康对照者,AUC 为 0.889,其中韦荣球菌属被鉴定为新型冠状病毒肺炎组的最显著生物标志物。韦荣球菌属的几个成员,特别是在我们的新型冠状病毒肺炎患者的口咽中高度富集的小韦荣球菌属,也在新型冠状病毒肺炎患者的 BALF 中过度表达,表明口腔是病原体的天然储库,可在新型冠状病毒肺炎患者的肺部引起合并感染。我们还发现,克雷伯菌属、不动杆菌属和沙雷氏菌属的增加比例与疾病严重程度和升高的全身炎症标志物(中性粒细胞-淋巴细胞比值,NLR)相关,表明这些口咽微生物群的改变可能通过影响炎症反应来影响新型冠状病毒肺炎的严重程度。此外,新型冠状病毒肺炎患者的口咽微生物群在氨基酸代谢和外来生物降解和代谢方面表现出显著的富集。此外,在新型冠状病毒肺炎组中检测到所有 26 种抗菌药物耐药基因类别的药物,在重症病例中显著富集。总之,我们发现口咽微生物群的改变和功能差异与新型冠状病毒肺炎的严重程度有关。