The resident gut microbiome modulates the effect of synbiotics on the immunogenicity after SARS-COV-2 vaccination in elderly and diabetes patients.

The study aims to tackle the seed and soil microbiome and mechanisms that contribute to the effect of synbiotics in enhancing immunogenicity after SARS-CoV-2 vaccination in elderly and diabetic patients. Among 369 subjects who received 3 months of SIM01, a gut microbiota-derived synbiotic formula of three Bifidobacterium strains (B. adolescentis, B. bididum, and B. longum) or a placebo after the SARS-CoV-2 vaccines (mRNA vaccine BNT162b2 (Pfizer-BioNTech) or the inactivated vaccine Sinovac-CoronaVac), we performed metagenomic sequencing in stool samples of 280 vaccinees collected at baseline and 3-month postvaccination and metabonomic sequencing in 276 vaccinees collected at baseline and 1-month postvaccination. The open niche of autochthonous gut microbiota (lower levels of Bifidobacterium and decreased functional potential for carbohydrate metabolism) was associated with enhancing SIM01-contained species. The enrichment of three bifidobacterial species after 3 months of SIM01 intervention (BABBBL_fc) was positively correlated with the level of neutralizing antibodies to the BNT162b2 vaccine at 6-month postvaccination. The fold change of benzoic acid was positively correlated with BABBBL_fc in the BNT162b2 vaccinees, which was also implicated with SARS-CoV-2 surrogate virus neutralization test (sVNT)% levels at 1-month postvaccination. Importantly, SIM01 strain engraftment assessed by StrainPhlAn (A metagenomic strain-level population genomics tool) was associated with a higher fold change of three bifidobacterial species and could be predicted based on the baseline gut microbiome. Therefore, the resident gut microbiome affected the SIM01 engraftment, which was associated with the immunogenicity of SARS-CoV-2 BNT162b2 vaccines.