Alterations of the Human Oral and Gut Microbiome and Lipid Metabonomics in COVID-19

COVID-19 has emerged as a global pandemic, resulting in over twenty million of infections and over half a million of death. However, the oral and gut microbiota, and lipid molecules characteristic in COVID-19 have not been studied clearly. Here, we collected and sequenced 392 tongue coating samples, 172 fecal samples, and 155 serum samples from different regions, times, and people. Compared with healthy controls (HC, stool, n=48; tongue coating, n=100), Haemophilus and Enterobacteriaceae_unclassifiedwere decreased, while Granulicatella increased in confirmed patients (CP, stool, n=24; tongue coat, n=48) at oral cavity and gut. The classifiers based on 8 optimal oral microbial markers (7 markers in gut microbiome) achieved good diagnostic efficiency and the area under the curve (AUC) reached 98.06% (99.74%) in discovery cohort and 95.75% (99.31%) in validation cohort. Importantly, the AUC reached 89.22% in extra diagnosis cohort from Hangzhou. Moreover, the classifiers successfully diagnosed suspected patients (SP) with IgG-antibody positivity as CP, and the AUC reached 92.11% (98.01%) and we have demonstrated the feasibility of this method from the perspective of microbial characteristic. Besides, with the recovery of COVID-19, among CP, CP recovery (CPR), and HC group,peptostreptococcaceae_incertae_sedis was gradually increased at oral cavity, but decreased at gut. Compared with CP, 47 lipid molecules including SM(d40:4), SM(d38:5), and MG(33:5) were depleted in the CPR group, 122 lipid molecules including PC(36:4p), PE(16:0p/20:5), and DG(20:1/18:2) were enriched in the CPR group. Fifty-two operational taxonomy units (OTU) in oral cavity (37 OTUs in gut) were correlated with 10 lipid molecules, and 68 OTUs in oral cavity (97 OTUs in gut) were correlated with 8 clinical indicators of COVID-19. In conclusion, we characterize the oral and gut microbiota and lipid in COVID-19, demonstrate the potential of microbial markers as non-invasive diagnostic tools for COVID-19 in different regions of China, make up the deficiency of nucleic acid testing, and search the specific therapeutic targets.