Royal jelly fermented by Lactobacillus panisapium M1 derived from honeybee queens (Apis mellifera L.) modulates plasmacytoid dendritic cell activation

Fermented royal jelly (fRJ) is generated via the complete bioconversion of the fatty acid 10-hydroxy-2-decenoic acid (10H2DA) into 10-hydroxydecanoic acid (10HDAA). This process occurs through fermentation with the lactic acid bacterium (LAB) <i>Lactobacillus panisapium</i> M1, which was isolated from honeybee queens (<i>Apis mellifera</i> L.). The resultant fRJ contains approximately fivefold higher levels of 10HDAA than RJ and demonstrated enhanced immunostimulatory activity. To further assess the immunological efficacy of fRJ, we performed <i>in vitro</i> assays using Flt3L-induced murine bone marrow-derived plasmacytoid dendritic cells (pDCs). fRJ treatment significantly upregulated activation markers MHC-II, CD86, CD80, and CD40 compared to RJ, with over two-fold higher expression levels. This effect was attributed, in part, to the activity of <i>L. panisapium</i> M1, whereas 10HDAA alone did not reproduce the same response. A pilot open-label clinical trial was conducted in healthy volunteers to evaluate the effect of fRJ on human pDC activation. After four weeks of daily fRJ intake, CD80 expression on peripheral blood pDCs increased by 1.1-fold compared to baseline. These findings suggest that fRJ has the potential to modulate host immune defense through pDC activation.