Specific gut microbiota were found to be markers for more favorable immune responses to and decreased rate of adverse effects from COVID-19 vaccination, according to study findings published in Gut.

For the prospective, observational study, researchers enrolled participants who had received the BNT162b2 mRNA (n=101) or CoronaVac inactivated (n=37) COVID-19 vaccine at the Prince of Wales Hospital of the Chinese University of Hong Kong or the Queen Mary Hospital of the University of Hong Kong between April and August 2021. Participants donated stool and blood samples within 3 days of the first dose of vaccine and at 1 month after the second dose of vaccine. Biomarkers for immune response to and adverse effects from vaccination were evaluated using metagenomic sequencing and serological testing approaches.

The study population had a median age of 47 (IQR, 31.2-55.0) years, 67.9% were women, 38.7% were considered overweight or had obesity, 40.4% had diarrhea in the past 3 months, and 38.7% had been vaccinated during the past year. The participants who received the mRNA vaccine were younger (median, 42 vs 55 years; P =.003).

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One month after the second dose, participants who had been vaccinated with the mRNA vaccine compared with CoronaVac had higher antibody response as measured by median surrogate virus neutralization test (sVNT; 95.2% vs 57.6%; P <.001), but more had adverse events after the first (93.0% vs 62.2%; P <.001) and second (95.0% vs 67.6%; P <.001) doses.

Baseline gut microbiome associated with comorbidities, antibiotic use during the past 3 months, regular exercise, and recent diarrhea.

Compared with baseline, at 1 month stool samples indicated a significant shift in beta diversity and decrease in alpha diversity. These patterns did not differ on the basis of vaccine formulation.

BNT162b2 recipients were observed to have increased Bacteroides caccae and Alistipes shahii; CoronaVac recipients had increased Bacteroides caccae. Other common species exhibited a relative decline. Changes in diversity did not associate with dietary intake among a subset of 72 randomly selected participants (P >.05).

The relative abundance of 7 and 15 bacterial species was observed to correlate with sVNT response to vaccination among BNT162b2 and CoronaVac recipients, respectively. After adjusting for age, Eubacterium rectale (r, 0.223; P =.026), Roseburia faecis (r, 0.215; P =.031), and Bacteroides thetaiotaomicron (r, 0.204; P =.042) predicted response for the BNT162b2 vaccine and Bifidobacterium adolescentis (r, 0.329; P =.050) for the CoronaVac vaccine.

For adverse effects, individuals who had an adverse effect after dose 1 were found to have significantly decreased bacterial species richness (P =.011). In a cluster analysis, participants who had a higher abundance of Prevotella copri and 2 Megamonas species at baseline were less likely to have adverse effects after vaccination.

These findings may not be generalizable, as the abundance of Prevotella copri has been associated with non-Western populations.

Overall, the study authors concluded that “baseline gut microbiota was significantly associated with immunogenicity and adverse events of COVID-19 vaccines. These novel findings have potential in facilitating microbiota-targeted interventions to optimize vaccine immune response and enhance durability of protection.”


Ng SC, Peng Y, Zhang L, et al. Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events. Gut. February 9, 2022. doi:10.1136/gutjnl-2021-326563