Potential interaction between the oral microbiota and COVID-19: a meta-analysis and bioinformatics prediction

Front Cell Infect Microbiol. 2023 Jun 7:13:1193340. doi: 10.3389/fcimb.2023.1193340. eCollection 2023.

Abstract

Objectives: The purpose of this study was to evaluate available evidence on the association between the human oral microbiota and coronavirus disease 2019 (COVID-19) and summarize relevant data obtained during the pandemic.

Methods: We searched EMBASE, PubMed, and the Cochrane Library for human studies published up to October 2022. The main outcomes of the study were the differences in the diversity (α and β) and composition of the oral microbiota at the phylum and genus levels between patients with laboratory-confirmed SARS-CoV-2 infection (CPs) and healthy controls (HCs). We used the Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA) database, Protein-protein interaction (PPI) network (STRING) and Gene enrichment analysis (Metascape) to evaluate the expression of dipeptidyl peptidase 4 (DPP4) (which is the cell receptor of SARS CoV-2) in oral tissues and evaluate its correlation with viral genes or changes in the oral microbiota.

Results: Out of 706 studies, a meta-analysis of 9 studies revealed a significantly lower alpha diversity (Shannon index) in CPs than in HCs (standardized mean difference (SMD): -0.53, 95% confidence intervals (95% CI): -0.97 to -0.09). Subgroup meta-analysis revealed a significantly lower alpha diversity (Shannon index) in older than younger individuals (SMD: -0.54, 95% CI: -0.86 to -0.23/SMD: -0.52, 95% CI: -1.18 to 0.14). At the genus level, the most significant changes were in Streptococcus and Neisseria, which had abundances that were significantly higher and lower in CPs than in HCs based on data obtained from six out of eleven and five out of eleven studies, respectively. DPP4 mRNA expression in the oral salivary gland was significantly lower in elderly individuals than in young individuals. Spearman correlation analysis showed that DPP4 expression was negatively correlated with the expression of viral genes. Gene enrichment analysis showed that DPP4-associated proteins were mainly enriched in biological processes, such as regulation of receptor-mediated endocytosis of viruses by host cells and bacterial invasion of epithelial cells.

Conclusion: The oral microbial composition in COVID-19 patients was significantly different from that in healthy individuals, especially among elderly individuals. DPP4 may be related to viral infection and dysbiosis of the oral microbiome in elderly individuals.

Keywords: COVID-19; SARS-CoV-2; bioinformatics prediction; meta-analysis; oral microbiota.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19*
  • Computational Biology
  • Dipeptidyl Peptidase 4
  • Humans
  • Microbiota* / genetics
  • SARS-CoV-2 / genetics

Substances

  • Dipeptidyl Peptidase 4

Grants and funding

This study was supported by the following funding sources: the National Natural Science Foundation of China (81800788 and 81773339), the Science and Technology Department of Hunan Province, China (2017WK2041, 2018SK52511, and 2022ZK4084), the Scientific Research Project of Hunan Provincial Health Commission (202208043514 and B202308056340), the Hunan Provincial Natural Science Foundation of China (2022JJ30062), the Natural Science Foundation of Changsha City (kq2202403 and kq2202412), the Fund for the Xiangya Clinical Medicine Database of Central South University (2014-ZDYZ-1-16), the Education and Teaching Reform Research Project of Central South University (2020jy165-3), the Research Project on Postgraduate Education and Teaching Reform of Central South University (2021JGB072), the Hunan Provincial Innovation Foundation For Postgraduate (CX20220370), and the Fundamental Research Funds for the Central Universities of Central South University (2022ZZTS0913 and 2022ZZTS0912).