Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events

• Published in: Gut Vol. 71; no. 6; pp. 1106 - 1116
• Main Authors: Ng, Siew C, Peng, Ye, Zhang, Lin, Mok, Chris KP, Zhao, Shilin, Li, Amy, Ching, Jessica YL, Liu, Yingzhi, Yan, Shuai, Chan, Dream L S, Zhu, Jie, Chen, Chunke, Fung, Adrian CH, Wong, Kenneth KY, Hui, David SC, Chan, Francis KL, Tun, Hein M
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.06.2022; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adult; Adverse events; Age; Alcohol use; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine; Body mass index; Carbohydrate metabolism; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - adverse effects; Diabetes; Drug dosages; enteric bacterial microflora; Enzyme-linked immunosorbent assay; Flagella; Gastrointestinal Microbiome; Gut microbiota; Humans; Hypertension; Immune response; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G; Infections; Inflammation; Intestinal microflora; Laboratories; Metagenomics; Microbiomes; Microbiota; mRNA; mRNA Vaccines; Obesity; Overweight; Pili; Probiotics; Prospective Studies; Questionnaires; SARS-CoV-2; Serology; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; Vaccines; Vaccines, Synthetic; Hong Kong China; United States > US; China; COVID-19; immune response; enteric bacterial microflora
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2021-326563

ObjectiveThe 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).DesignWe 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.ResultsWe 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).ConclusionOur 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.