AUTHOR=Otaegui-Chivite Ane , Gorostidi-Aicua Miriam , Martins-Almeida Laura , Alberro Ainhoa , Romarate Leire , Mendiburu Idoia , Álvarez de Arcaya Amaya , Arruti Maialen , Castillo-Triviño Tamara , Otaegui David , Moles Laura TITLE=Exploring the mycobiota in multiple sclerosis: its influence on disease development and progression JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1625794 DOI=10.3389/fimmu.2025.1625794 ISSN=1664-3224 ABSTRACT=BackgroundMultiple sclerosis (MS) is a complex immune-mediated disorder influenced by genetic, environmental, and microbial factors. Recent research has focused on the gut microbiota’s role in MS, yet limited studies have examined the fungal microbiota (mycobiota) in this context.MethodsIn this study, we characterized the gut mycobiota of individuals with MS from the Basque Country, identifying specific fungal taxa associated with MS risk factors, clinical severity, and dietary patterns.ResultsOur results revealed higher fungal diversity and richness in MS patients compared to controls, with significant enrichment of certain genera, including Saccharomyces, Torulaspora, and Malassezia. Malassezia demonstrated a strong association with increased disability, aligning with its previous identification in neurodegenerative conditions. Furthermore, we found that the presence of the MS-associated allele HLA-DRB1*1501 significantly influenced mycobiota composition and correlated with disability metrics. Additionally, we observed a complex interplay between plasma biomarkers (chitotriosidase and calprotectin) and specific fungal groups, with disease-specific correlations indicating potential interactions between the immune response and gut fungi. Notably, dietary fats showed a greater impact on mycobiota composition in MS patients than in controls, highlighting altered lipid metabolism in MS.ConclusionThese findings provide new insights into the fungal component of the gut microbiota in MS and underscore its potential role in disease pathogenesis and progression. Our work suggests that fungal biomarkers, together with genetic and dietary factors, may help refine our understanding of MS and support the development of mycobiota-targeted therapies.