Candida intermedia Supplementation Enhances Immune Response and Modulates the Gut Microbiome in SARS-CoV-2 Vaccinated Mice

Non-<i>Saccharomyces</i> yeasts are emerging as promising new probiotics with a beneficial effect equal to or greater than the reference probiotic yeast, <i>Saccharomyces boulardii</i>. <i>Candida intermedia</i>, a non-<i>albicans</i> species not considered a common human pathogen, previously demonstrated probiotic potential. In this work, our objective was to evaluate the immunomodulatory effects of <i>C. intermedia</i> ORQ001 in mice vaccinated with inactivated SARS-CoV-2, seeking further evidence of its probiotic activity. Murine macrophages were stimulated with <i>C. intermedia</i>, followed by mRNA transcription analysis via qPCR. Mice were supplemented with <i>C. intermedia</i> prior to SARS-CoV-2 vaccination. Antibody production was assessed by ELISA, and fecal microbiomes were analyzed using next-generation sequencing. <i>C. intermedia</i> significantly increased <i>Il4</i> and <i>Il13</i> expression while decreasing <i>Stat3</i> in macrophages. Splenocytes from supplemented mice exhibited elevated transcription levels of <i>Tnf</i>, <i>Ifng</i>, <i>Il4</i>, <i>Bcl6</i>, and <i>Stat3</i> after exposure to stimulatory molecules. These mice showed increased levels of anti-SARS-CoV-2 IgG and sIgA isotypes, along with higher abundances of <i>Bacteroides</i> spp. and <i>Clostridium</i> spp. in their gut microbiome. In conclusion, <i>C. intermedia</i> supplementation modulated the expression of key immune-related genes and enhanced humoral responses in mice. Furthermore, its influence on gastrointestinal microbiota suggests a synergistic effect on vaccine immunogenicity. These findings support the potential of <i>C. intermedia</i> as a novel probiotic candidate with immunomodulatory properties applicable to vaccine adjuvanticity.