Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Guang-Ying Cui; Ben-Chen Rao; Zhao-Hai Zeng; Xue-Mei Wang; Tong Ren; Hai-Yu Wang; Hong Luo; Hong-Yan Ren; Chao Liu; Su-Ying Ding; Jun-Jie Tan; Zhen-Guo Liu; Ya-Wen Zou; Zhi-Gang Ren; Zu-Jiang Yu

doi:10.1186/s40779-022-00387-y

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Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

RESEARCH | Updated：2023-05-10

- Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up
- Military Medical Research Vol. 10, Issue 2, Pages: 162-174(2023)
- Affiliations：
  
  1.Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  2.Gene Hospital of Henan Province/Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  3.Department of Infectious Diseases, Guangshan County People's Hospital, Guangshan County, Xinyang 465450, Henan, China
  4.Department of Breast Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450052, China
  5.Shanghai Mobio Biomedical Technology Co., Ltd, Shanghai 201111, China
  6.Health Management Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Author bio：
  
  * fccrenzg@zzu.edu.cn;
  johnyuem@zzu.edu.cn
- Funds：
- DOI：10.1186/s40779-022-00387-y
  CLC：
- Published：2023-04
- Accepted：
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Cite this article as: Cui GY, Rao BC, Zeng ZH, Wang XM, Ren T, Wang HY, et al. Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up. Mil Med Res. 2022;9(1):32.
DOI：

Cite this article as: Cui GY, Rao BC, Zeng ZH, Wang XM, Ren T, Wang HY, et al. Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up. Mil Med Res. 2022;9(1):32. DOI： 10.1186/s40779-022-00387-y.

摘要

Abstract

Background:

Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19)

more than 160 million patients have become convalescents worldwide to date. 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 1-year recovery.

Methods:

We recruited 35 confirmed patients to provide 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

129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing

and plasma samples were subjected to untargeted metabolomics testing.

Results:

The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process

the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased

whereas lipopolysaccharide-producing microbes gradually decreased. In addition

sphingosine-1-phosphate

which is closely related to the inflammatory factor storm of COVID-19

increased significantly during the recovery process. Moreover

the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later.

Conclusions:

This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified

and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

关键词

Keywords

references

World Health Organization . Coronavirus disease (COVID-19) Weekly epidemiological update and Weekly operational update , 2020 . Available: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/.2020 https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/.2020 .

O’Dowd A . Covid-19: third of people infected have long term symptoms . BMJ. 2021 ; 373 : n1626 .

Nehme M , Braillard O , Chappuis F , Courvoisier DS , Guessous I . CoviCare study team. Prevalence of symptoms more than seven months after diagnosis of symptomatic COVID-19 in an outpatient setting . Ann Intern Med. 2021 ; 174 ( 9 ): 1252 – 60 .

Blomberg B , Mohn KG , Brokstad KA , Zhou F , Linchausen DW , Hansen BA , et al . Long COVID in a prospective cohort of home-isolated patients . Nat Med. 2021 ; 27 ( 9 ): 1607 – 13 .

Osmanov IM , Spiridonova E , Bobkova P , Gamirova A , Shikhaleva A , Andreeva M , et al . Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study . Eur Respir J. 2022 ; 59 ( 2 ): 2101341 .

Huang C , Huang L , Wang Y , Li X , Ren L , Gu X , et al . 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study . Lancet. 2021 ; 397 ( 10270 ): 220 – 32 .

Wang W , Yan Y , Guo Z , Hou H , Garcia M , Tan X , et al . All around suboptimal health-a joint position paper of the suboptimal health study consortium and European Association for predictive preventive and personalised medicine . EPMA J. 2021 ; 12 ( 4 ): 403 – 33 .

Wang LY , Cui JJ , Ouyang QY , Zhan Y , Wang YM , Xu XY , et al . Complex analysis of the personalized pharmacotherapy in the management of COVID-19 patients and suggestions for applications of predictive, preventive, and personalized medicine attitude . EPMA J. 2021 ; 12 ( 3 ): 307 – 24 .

Ren Z , Wang H , Cui G , Lu H , Wang L , Luo H , et al . Alterations in the human oral and gut microbiomes and lipidomics in COVID-19 . Gut. 2021 ; 70 ( 7 ): 1253 – 65 .

Yeoh YK , Zuo T , Lui GC , Zhang F , Liu Q , Li AY , et al . Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19 . Gut. 2021 ; 70 ( 4 ): 698 – 706 .

Zuo T , Zhang F , Lui GCY , Yeoh YK , Li AYL , Zhan H , et al . Alterations in gut microbiota of patients with COVID-19 during time of hospitalization . Gastroenterology. 2020 ; 159 ( 3 ): 944-55.e8 .

Weiss RH , Kim K . Metabolomics in the study of kidney diseases . Nat Rev Nephrol. 2011 ; 8 ( 1 ): 22 – 33 .

Beyoğlu D , Idle JR . The metabolomic window into hepatobiliary disease . J Hepatol. 2013 ; 59 ( 4 ): 842 – 58 .

Ussher JR , Elmariah S , Gerszten RE , Dyck JR . The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease . J Am Coll Cardiol. 2016 ; 68 ( 25 ): 2850 – 70 .

Shen B , Yi X , Sun Y , Bi X , Du J , Zhang C , et al . Proteomic and metabolomic characterization of COVID-19 patient sera . Cell. 2020 ; 182 ( 1 ): 59-72.e15 .

Song JW , Lam SM , Fan X , Cao WJ , Wang SY , Tian H , et al . Omics-driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis . Cell Metab. 2020 ; 32 ( 2 ): 188-202.e5 .

Ren Z , Li A , Jiang J , Zhou L , Yu Z , Lu H , et al . Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma . Gut. 2019 ; 68 ( 6 ): 1014 – 23 .

Edgar RC . UPARSE: highly accurate OTU sequences from microbial amplicon reads . Nat Methods. 2013 ; 10 ( 10 ): 996 – 8 .

Wang Q , Garrity GM , Tiedje JM , Cole JR . Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy . Appl Environ Microbiol. 2007 ; 73 ( 16 ): 5261 – 7 .

Tan CW , Chia WN , Qin X , Liu P , Chen MI , Tiu C , et al . A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction . Nat Biotechnol. 2020 ; 38 ( 9 ): 1073 – 8 .

Qian C , Zhou M , Cheng F , Lin X , Gong Y , Xie X , et al . Development and multicenter performance evaluation of fully automated SARS-CoV-2 IgM and IgG immunoassays . Clin Chem Lab Med. 2020 ; 58 ( 9 ): 1601 – 7 .

Marfia G , Navone S , Guarnaccia L , Campanella R , Mondoni M , Locatelli M , et al . Decreased serum level of sphingosine-1-phosphate: a novel predictor of clinical severity in COVID-19 . EMBO Mol Med. 2021 ; 13 ( 1 ): e13424 .

Frost F , Kacprowski T , Rühlemann M , Pietzner M , Bang C , Franke A , et al . Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function . Gut. 2021 ; 70 ( 3 ): 522 – 30 .

Tachalov VV , Orekhova LY , Kudryavtseva TV , Loboda ES , Pachkoriia MG , Berezkina IV , et al . Making a complex dental care tailored to the person: population health in focus of predictive, preventive and personalised (3P) medical approach . EPMA J. 2021 ; 12 ( 2 ): 129 – 40 .

Zhan X , Li J , Guo Y , Golubnitschaja O . Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine . EPMA J. 2021 ; 12 ( 4 ): 449 – 75 .

Rosen H , Oldstone MBA . The riddle of the Sphinx: why sphingosine-1-phosphate may help define molecular mechanisms underlying risk stratification for serious COVID-19 infections . EMBO Mol Med. 2021 ; 13 ( 1 ): e13533 .

Huang C , Wang Y , Li X , Ren L , Zhao J , Hu Y , et al . Clinical features of patients infected with 2019 novel coronavirus in Wuhan . China Lancet. 2020 ; 395 ( 10223 ): 497 – 506 .

Hänel P , Andréani P , Gräler MH . Erythrocytes store and release sphingosine 1-phosphate in blood . FASEB J. 2007 ; 21 ( 4 ): 1202 – 9 .

Streetz KL , Wüstefeld T , Klein C , Manns MP , Trautwein C . Mediators of inflammation and acute phase response in the liver . Cell Mol Biol (Noisyle-grnd). 2021 ; 47 ( 4 ): 661 – 73 .

Christensen PM , Bosteen MH , Hajny S , Nielsen LB , Christoffersen C . Apolipoprotein M mediates sphingosine-1-phosphate efflux from erythrocytes . Sci Rep. 2017 ; 7 ( 1 ): 14983 .

McGowan EM , Haddadi N , Nassif NT , Lin Y . Targeting the SphK-S1P-SIPR pathway as a potential therapeutic approach for COVID-19 . Int J Mol Sci. 2020 ; 21 ( 19 ): 7189 .

Törnquist K , Asghar MY , Srinivasan V , Korhonen L , Lindholm D . Sphingolipids as modulators of SARS-CoV-2 infection . Front Cell Dev Biol. 2021 ; 9 : 689854 .

Zhang X , Zhang D , Jia H , Feng Q , Wang D , Liang D , et al . The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment . Nat Med. 2015 ; 21 ( 8 ): 895 – 905 .

Chen C , Hemme C , Beleno J , Shi ZJ , Ning D , Qin Y , et al . Oral microbiota of periodontal health and disease and their changes after nonsurgical periodontal therapy . ISME J. 2018 ; 12 ( 5 ): 1210 – 24 .

Sanders ME , Merenstein DJ , Reid G , Gibson GR , Rastall RA . Probiotics and prebiotics in intestinal health and disease: from biology to the clinic . Nat Rev Gastroenterol Hepatol. 2019 ; 16 ( 10 ): 605 – 16 .

Sanna S , van Zuydam NR , Mahajan A , Kurilshikov A , Vich Vila A , Vosa U , et al . Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases . Nat Genet. 2019 ; 51 ( 4 ): 600 – 5 .

Fan Y , Pedersen O . Gut microbiota in human metabolic health and disease . Nat Rev Microbiol. 2021 ; 19 ( 1 ): 55 – 71 .

Chen Y , Gu S , Chen Y , Lu H , Shi D , Guo J , et al . Six-month follow-up of gut microbiota richness in patients with COVID-19 . Gut. 2022 ; 71 ( 1 ): 222 – 5 .

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