Dynamic Alterations Of Oral And Gut Microbiome And Plasma Metabolomic Characteristics In COVID-19 Convalescents

BackgroundSince the outbreak of the new coronavirus pneumonia(Corona Virus Disease 2019,COVID-19),as of March 1,2022,the cumulative number of confirmed cases in the world has exceeded 430 million,and the cumulative number of cured people has exceeded 360 million.The pathophysiological changes caused by COVID-19 can have long-term effects on the body and cause persistent symptoms.Studies have shown that critically ill patients with COVID-19 still have symptoms of severe lung damage up to 3 months after they are discharged from the hospital.A 6-month follow-up of COVID-19 patients found that symptoms such as fatigue,sleep disturbances,sensory disturbances,and dyspnea also frequently appeared.Therefore,it is of great clinical significance to continue to pay attention to the health status of patients who have recovered from COVID-19 and try to improve the complications and sequelae caused by COVID-19.Alterations in the human microbiome and metabolomics are closely related to a variety of diseases,and they play important roles in regulating human digestion and absorption,immune response,and metabolism.Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19.However,it is unknown whether their characteristics return to normal after the one-year recovery.In addition,the correlations between the microbiome and metabolites and how they influence the recovery of COVID-19 are also unknown.ObjectiveThis study was aimed to characterize the oral microbiome,gut microbiome,and plasma metabonomics profile in one-year convalescents of COVID-19.Then,we identified the key microbiome and metabolites in the process of recovery and evaluate the potential of the microbiome and metabolites as predictive markers and explore correlations between the microbiome and metabolites profile.MethodsWe recruited 35 confirmed patients to leave specimens at discharge and 1 year later,as well as 160 healthy controls.A total of 497 samples were prospectively collected,including 219 tongue-coating samples,129 stool samples and 149 plasma samples.Tongue-coating and stool samples were conducted 16S rRNA Mesiq sequencing,and plasma samples were performed the untargeted metabolomics testing.ResultsCompared with patients at the time of discharge,the oral and gut microbiome and metabolomics characteristics of the one-year convalescents have been restored to a large extent but have not completely returned to normal.In the recovery process of COVID-19,the diversity of the oral and gut microbiome gradually increased.Butyric acid-producing microbes and probiotics gradually increased,whereas lipopolysa ccharide-producing microbes gradually decreased.Then,during the recovery process,the abundances of PE(15:0/16:1(9Z)),tryptophan betaine and catechol sulfate gradually increased,while the abundances of(±)18-HEPE,Quinquenoside F1 and 5(S)-HpETE gradually decreased in the plasma.In addition,Sphingosine1-phosphate(SIP)which is closely related to the inflammatory factor storm of COVID-19 increased significantly during the recovery process.Furthermore,the one year later neutralizing antibody prediction model established based on the oral and gut microbiome and plasma metabolites at the time of discharge of the diagnosed patients achieved the prediction efficiency of 90.48%,85.71%and 87.04%,respectively.Finally,the Spearman correlation analysis on key oral and gut microbiome and plasma metabolites during recovery process showed that the abundance of S1P was positively correlated with Faecalibacterium,Bifidobacterium and Lachnospira in the faeca and Peptostreptococcus and Streptococcus in the tongue coating.On the contrary,the abundance of S1P was negatively correlated with Burkholderiales in the tongue coating.ConclusionThis study is the first to characterize the oral and gut microbiome and metabonomics in one-year convalescents of COVID-19,and identify the key microbiome and metabolites in the process of recovery.In addition,the predictive models based on the microbiome and metabolomics afford new tools for predicting the neutralizing antibody of COVID-19 convalescents.This study provided novel targets and strategies to promote the recovery of COVID-19.