Exploring the Mycobiota in Multiple Sclerosis: Its Influence on Disease Development and Progression

Ane Otaegui¹Miriam Gorostidi Aicua¹Laura Martins Almeida¹Ainhoa Alberro Garitano¹Leire Romarate García¹Idoia Mendiburu Arrieta²Amaya Álvarez de Arcaya³Maialen Arruti Gonzalez²Tamara Castillo Triviño²David Otaegui^1*Laura Moles Alegre^1*

• ¹Biogipuzkoa Health Research Institute, San Sebastián-Donostia, Spain
• ²Hospital Universitario Donostia, San Sebastián-Donostia, Spain
• ³Hospital Universitario Araba, Vitoria, Spain

Background: Multiple 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.Methods: In 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.Results: Our 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.Conclusion: These 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.