IDDF2024-ABS-0278 Integrative multi-omics reveal associations between gut microbiome and immune response against COVID-19 vaccine in the elderly

<h3>Background</h3> Several recent studies suggested that gut microbiota are crucial in modulating immune responses to COVID-19 vaccination. However, the majority of these studies have focused on younger populations, and the effects of gut microbiota on COVID-19 vaccine-induced immune responses in the elderly remain elusive. <h3>Methods</h3> We recruited 25 subjects (aged 64-86 years) who required the fourth dose of a recombinant COVID-19 vaccine (ZF2001) for multi-omics analysis, including metagenomics, metabolomics, single-cell RNA sequencing (scRNA-seq), single-cell T-cell receptor/B-cell receptor sequencing (scTCR/BCR-seq). And mendelian randomisation (MR) was applied to analyse the causal relationship between gut microbiota and plasma phosphatidylcholines (PCs) (IDDF2024-ABS-0278 Figure 1. Research design and data collection diagram). <h3>Results</h3> Elevations in the levels of the <i>Bifidobacterium</i> genus, specifically <i>B. dentium</i> and <i>B. pseudocatenulatum</i>, were detected in the fecal samples of the high-response group. Notably, these <i>Bifidobacterium</i> species revealed a correlation with the ratio of neutralizing antibodies measured on Day 28 compared to Day 0. Furthermore, untargeted metabolomics analysis revealed that the upregulated differential fecal metabolites in the high-response group predominantly consisted of PCs, exhibiting an approximately tenfold increase in abundance. Moreover, the results of MR revealed that <i>Bifidobacterium</i> had an effect on PCs, well confirming the association between <i>Bifidobacterium</i> and PCs. Flow cytometric analysis revealed that the CD4/CD8 ratio is upregulated in the low-response group, indicating an elevated level of immunosenescence. scRNA-seq data further validated the immunosenescent status of the low-response group. scRNA-seq showed that the percentages of Naive B cells were lower (<i>P</i>&lt;0.05) and Non-switched memory B cells were higher in the low response group (<i>P</i>&lt;0.05). Meanwhile, single-cell immune repertoire analysis showed that the total clone of TCRβ-CDR3 against 6 viruses increased in the high response group (<i>P</i>&lt;0.05). <h3>Conclusions</h3> Multi-omics analyses showed lower immunosenescence in the high response group, accompanied by increased intestinal <i>B.dentium</i> and <i>B.pseudocatenulatum</i> as well as PCs. The potential utility of <i>Bifidobacterium</i> and phosphatidylcholines (PCs) as functional foods to enhance COVID-19 vaccination efficacy in immunosenescent elders requires further investigation.