Article Text
PDF
Abstract
Background 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.
Methods 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).
Results Elevations in the levels of the Bifidobacterium genus, specifically B. dentium and B. pseudocatenulatum, were detected in the fecal samples of the high-response group. Notably, these Bifidobacterium 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 Bifidobacterium had an effect on PCs, well confirming the association between Bifidobacterium 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 (P<0.05) and Non-switched memory B cells were higher in the low response group (P<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 (P<0.05).
Research design and data collection diagram
Conclusions Multi-omics analyses showed lower immunosenescence in the high response group, accompanied by increased intestinal B.dentium and B.pseudocatenulatum as well as PCs. The potential utility of Bifidobacterium and phosphatidylcholines (PCs) as functional foods to enhance COVID-19 vaccination efficacy in immunosenescent elders requires further investigation.