Human microbiota dysbiosis after SARS-CoV-2 infection have the potential to predict disease prognosis

Abstract

Abstract Background The studies on SARS-CoV-2 and human microbiota have yielded inconsistent results regarding microbiota α-diversity and key microbiota. To address these issues and explore the predictive ability of human microbiota for the prognosis of SARS-CoV-2 infection, we conducted a reanalysis of existing studies. Methods We reviewed the existing studies on SARS-CoV-2 and human microbiota in the Pubmed and Bioproject databases (from inception through October 29, 2021) and extracted the available raw 16S rRNA sequencing data of human microbiota. Firstly, we used meta-analysis and bioinformatics methods to reanalyze the raw data and evaluate the impact of SARS-CoV-2 on human microbial α-diversity. Secondly, machine learning (ML) was employed to assess the ability of microbiota to predict the prognosis of SARS-CoV-2 infection. Finally, we aimed to identify the key microbiota associated with SARS-CoV-2 infection. Results A total of 20 studies related to SARS-CoV-2 and human microbiota were included, involving gut (n = 9), respiratory (n = 11), oral (n = 3), and skin (n = 1) microbiota. Meta-analysis showed that in gut studies, when limiting factors were studies ruled out the effect of antibiotics, cross-sectional and case–control studies, Chinese studies, American studies, and Illumina MiSeq sequencing studies, SARS-CoV-2 infection was associated with down-regulation of microbiota α-diversity (P < 0.05). In respiratory studies, SARS-CoV-2 infection was associated with down-regulation of α-diversity when the limiting factor was V4 sequencing region (P < 0.05). Additionally, the α-diversity of skin microbiota was down-regulated at multiple time points following SARS-CoV-2 infection (P < 0.05). However, no significant difference in oral microbiota α-diversity was observed after SARS-CoV-2 infection. ML models based on baseline respiratory (oropharynx) microbiota profiles exhibited the ability to predict outcomes (survival and death, Random Forest, AUC = 0.847, Sensitivity = 0.833, Specificity = 0.750) after SARS-CoV-2 infection. The shared differential Prevotella and Streptococcus in the gut, respiratory tract, and oral cavity was associated with the severity and recovery of SARS-CoV-2 infection. Conclusions SARS-CoV-2 infection was related to the down-regulation of α-diversity in the human gut and respiratory microbiota. The respiratory microbiota had the potential to predict the prognosis of individuals infected with SARS-CoV-2. Prevotella and Streptococcus might be key microbiota in SARS-CoV-2 infection.

Keywords

• SARS-CoV-2/COVID-19
• Human microbiota
• α-diversity
• Key microbiota
• Machine learning