Boosting HSA Vaccination with Jujube Powder Modulating Gut Microbiota Favorable for Arginine Metabolism

Whereas vaccination is established as one of the most effective and available methods against seasonal flu and holds high potential for many infectious diseases, immune response may differ among individuals and regions. In this study we examined the effects of gut microbiota on vaccination with human serum albumin (HSA) as the model vaccine in C57BL/6J mice. We observed that a two-week antibiotic cocktail (ABX) treatment hampered HSA-specific IgG1 in serum, whereas fecal microbiota transplantation (FMT) restored the gut microbiota impaired by the ABX treatment and consequently increased the proportions of macrophages in the mesenteric lymph nodes (MLNs), plasma cells in the peripheral blood, and HSA-specific immunoglobulin G1 (IgG1) in the serum. A week of daily application of jujube powder (800 mg/kg) to ABX-treated mice achieved a significantly higher HSA-specific IgG1 concentration in the serum compared with the ABX treatment group. Of particular note was that the administration of the jujube powder did not increase the myeloid cells, indicating a different mechanism of vaccination compared with FMT. More interestingly, daily pre-administration of jujube powder (800 mg/kg) to healthy mice one week ahead of vaccination boosted their immune response, as evidenced by the proportion of macrophages in the MLNs, B cells in the spleen, plasma cells and memory B cells in the peripheral blood, and HSA-specific IgG1 concentration in the serum. The 16S rRNA sequencing of gut microbiota revealed that the administration of jujube powder increased the abundance of Coriobacteriaceae associated with the metabolism of amino acids. The Kyoto encyclopedia of genes and genomes (KEGG) analysis suggested the altered microbiota is more favorable for arginine and proline metabolism, which may promote macrophages in the MLNs. These results indicate a high potential for boosting vaccination by manipulating gut microbiota with natural products.