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Gut microbiota
Original research
Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19
  1. Yun Kit Yeoh1,2,
  2. Tao Zuo2,3,4,
  3. Grace Chung-Yan Lui3,5,
  4. Fen Zhang2,3,4,
  5. Qin Liu2,3,4,
  6. Amy YL Li3,
  7. Arthur CK Chung2,3,4,
  8. Chun Pan Cheung2,3,4,
  9. Eugene YK Tso6,
  10. Kitty SC Fung7,
  11. Veronica Chan6,
  12. Lowell Ling8,
  13. Gavin Joynt8,
  14. David Shu-Cheong Hui3,5,
  15. Kai Ming Chow3,
  16. Susanna So Shan Ng3,5,
  17. Timothy Chun-Man Li3,5,
  18. Rita WY Ng1,
  19. Terry CF Yip3,4,
  20. Grace Lai-Hung Wong3,4,
  21. Francis KL Chan2,3,4,
  22. Chun Kwok Wong9,
  23. Paul KS Chan1,2,10,
  24. Siew C Ng2,3,4
  1. 1Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong
  2. 2Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
  3. 3Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
  4. 4State Key Laboratory for digestive disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong
  5. 5Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
  6. 6Department of Medicine and Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong
  7. 7Department of Pathology, United Christian Hospital, Kwun Tong, Hong Kong
  8. 8Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong
  9. 9Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong
  10. 10Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
  1. Correspondence to Professor Siew C Ng, Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong; siewchienng{at}cuhk.edu.hk

Abstract

Objective Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.

Methods In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.

Results Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.

Conclusion Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

  • colonic microflora
  • inflammation
  • colonic bacteria

Data availability statement

Data are available in a public, open access repository. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA650244. Raw sequence data are available in the Sequence Read Archive (SRA) under BioProject accession PRJNA650244.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/gutjnl-2020-323020

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    Data availability statement

    Data are available in a public, open access repository. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA650244. Raw sequence data are available in the Sequence Read Archive (SRA) under BioProject accession PRJNA650244.

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    Footnotes

    • PKC and SCN are joint senior authors.

    • Twitter @Tao_Zuo_, @Siew_C_Ng

    • YKY, TZ and CKW contributed equally.

    • Contributors SCN, GC-YL, ET, KSCF, VC, LL recruited study subjects. AYLL, RWYN, TCFY, GL-HW procured and collated patients’ clinical data. PC organised sample inventory and processing. TZ, QL, FZ, AC, CPC performed laboratory work including extracting DNA and generating sequence data. CKW performed cytokine and chemokine measurements. YKY and SCN analyzed and interpreted the data, and wrote the manuscript. GJ, DS-CH and other authors reviewed the manuscript. SCN, PC and FKLC designed and supervised the study.

    • Funding This study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (COVID190111), and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.