Non-conventional yeasts with the potential to bridge probiotic and parabiotic applications in foods and dietary supplements: genomics and human model interaction

• Phylogenetic proximity to pro-technological and probiotic yeasts; • A few genes associated with flocculation and adhesion were found; • No high-similarity matches for potential antimicrobial resistance genes; • Modulation of inflammatory responses in Caco-2 cells, PBMC, and Keratinocytes; • Phytase activity under simulated gastrointestinal conditions. This study was aimed to evaluate the suitability of Lachancea fermentati, Lachancea thermotolerans , and Saccharomyces uvarum strains for possible use in health-promoting formulations. We also sought to address key knowledge gaps concerning their genomic characteristics and safety profiles. Phylogenetic multi-locus analysis, together with the inspection of genomic annotations and a similarity search, confirmed the close relationship of these species with a group of yeasts renowned for their technological and probiotic properties, placing them in a distinct clade from pathogenic yeasts. The genome annotation and a subsequent similarity search approach led to find genes or sequence traces related to flocculation, adhesion and biofilm formation, and no high-similarity matches were found for potential antimicrobial resistance genes. Although our results are limited by the absence of a transcriptomics experiment, the three strains showed an abundance of genes involved in several KEGG pathways that are potentially related to the immunomodulatory properties of the yeast cell wall. S. uvarum SERIUS and, to a lesser extent, L. thermotolerans LT3 were effective in alleviating inflammatory and oxidative processes in various cellular models, including Caco-2 cells, PBMC and human keratinocytes. The phytase activity exhibited by the yeasts under simulated gastrointestinal conditions highlights their potential as a source of enzymes capable of enhancing nutrient absorption in humans. Their limited growth at 37°C might further support a low risk of human pathogenicity. Although further experiments are needed to ascertain the functional and safety profiling, taken together, these traits indicate a possible use in health-promoting applications.