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COVID-19
Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events
  1. Siew C Ng1,2,3,4,
  2. Ye Peng5,6,
  3. Lin Zhang1,2,4,7,
  4. Chris KP Mok3,8,
  5. Shilin Zhao5,6,
  6. Amy Li1,
  7. Jessica YL Ching1,
  8. Yingzhi Liu4,7,
  9. Shuai Yan4,7,
  10. Dream L S Chan4,
  11. Jie Zhu5,6,
  12. Chunke Chen3,8,
  13. Adrian CH Fung9,
  14. Kenneth KY Wong9,
  15. David SC Hui1,10,
  16. Francis KL Chan1,2,3,4,
  17. Hein M Tun5,6
  1. 1Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
  2. 2State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
  3. 3Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
  4. 4Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China
  5. 5HKU-Pasteur Research Pole, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  6. 6School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  7. 7Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University Hong Kong, Hong Kong SAR, China
  8. 8Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
  9. 9Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  10. 10Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
  1. Correspondence to Dr Hein M Tun, HKU-Pasteur Research Pole, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; heinmtun{at}hku.hk; Professor Francis KL Chan, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; fklchan{at}cuhk.edu.hk

Abstract

Objective The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty).

Design We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination. Immune markers were measured by SARS-CoV-2 surrogate virus neutralisation test and spike receptor-binding domain IgG ELISA.

Results We found a significantly lower immune response in recipients of CoronaVac than BNT162b2 vaccines (p<0.05). Bifidobacterium adolescentis was persistently higher in subjects with high neutralising antibodies to CoronaVac vaccine (p=0.023) and their baseline gut microbiome was enriched in pathways related to carbohydrate metabolism (linear discriminant analysis (LDA) scores >2 and p<0.05). Neutralising antibodies in BNT162b2 vaccinees showed a positive correlation with the total abundance of bacteria with flagella and fimbriae including Roseburia faecis (p=0.028). The abundance of Prevotella copri and two Megamonas species were enriched in individuals with fewer adverse events following either of the vaccines indicating that these bacteria may play an anti-inflammatory role in host immune response (LDA scores>3 and p<0.05).

Conclusion Our study has identified specific gut microbiota markers in association with improved immune response and reduced adverse events following COVID-19 vaccines. Microbiota-targeted interventions have the potential to complement effectiveness of COVID-19 vaccines.

  • immune response
  • COVID-19
  • enteric bacterial microflora

Data availability statement

Data are available in a public, open access repository. Quality-controlled and human DNA-removed sequence data are deposited in the European Nucleotide Archive under BioProject PRJEB48269. Additional datasets generated and/or analysed in this study are available from the corresponding author on reasonable request.

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/.

http://dx.doi.org/10.1136/gutjnl-2021-326563

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    Data availability statement

    Data are available in a public, open access repository. Quality-controlled and human DNA-removed sequence data are deposited in the European Nucleotide Archive under BioProject PRJEB48269. Additional datasets generated and/or analysed in this study are available from the corresponding author on reasonable request.

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    Footnotes

    • Twitter @Siew_C_Ng, @YePeng21, @linzhang8385, @hk_kennethwong, @FrancisKLChan, @thetunlab

    • SCN, YP and LZ contributed equally.

    • Contributors SCN, LZ, CKPM, FKLC and HMT conceived and designed the study. CKPM and CC carried out serology testing and analysis. AYL, SZ, YP, SY and DLSC recruited participants, JYLC executed clinical protocols. HMT, YP, SZ and JZ performed bioinformatic and statistical analyses. SCN, YP, LZ, CKPM, FKLC and HMT wrote the manuscript with input from all co-authors. HMT acts as the guarantor for this study and publication.

    • Funding The project was supported by the Health and Medical Research Fund (HMRF) Commissioned Research Grant (COVID193002) (FKLC); Enhanced start-up research grant of HKU and RGC Research Impact Fund (R7033-18) (HMT) and the National Research Foundation of Korea (NRF) grant funded through the Korea government (NRF-2018M3A9H4055203) (KPM).

    • Competing interests The Chinese University of Hong Kong and The University of Hong Kong have filed a provisional patent application in connection with this work on which SCN, FKLC and HMT are inventors (US patent application no. 63/273,088). FKLC and SCN are the scientific co-founders and sit in the board of Directors of GenieBiome Ltd.

    • 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.