Background: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2. Methods: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis. Results: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2–59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint.
Streptococcus parasanguinis (log
10LDA score = 2.38,
p = 0.003; relative abundance of 2.97 × 10
−5 vs. 0.03%,
p = 0.001),
Bacteroides stercoris (log
10LDA score = 4.29,
p = 0.024; relative abundance of 0.14% vs. 2.40%,
p = 0.014) and
Haemophilus parainfluenzae (log
10LDA score = 2.15,
p = 0.022; relative abundance of 0.01% vs. 0,
p = 0.010) were enriched in low responders.
Bifidobacterium pseudocatenulatum (log
10LDA score = 2.99,
p = 0.048; relative abundance of 0.09% vs. 0.36%,
p = 0.049) and
Clostridium leptum (log
10LDA score = 2.38,
p = 0.014; relative abundance of 1.2 × 10
−5% vs. 0,
p = 0.044) were enriched in high responders.
S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log
10LDA score = 2.63), which contributes to inflammation and antibody production.
H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log
10LDA score = 2.14). Conclusion: Among three-dose BNT162b2 recipients,
S. parasanguinis,
B. stercoris and
H. parainfluenzae were associated with poorer immunogenicity at one year, while
B. pseudocatenulatum and
C. leptum was associated with a better response.
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