Resumen: There is growing evidence of the involvement of gut microbiota in neurodegenerative diseases. However, the relationship between gut microbiota and prion diseases is not yet well understood. Prion diseases are neurodegenerative disorders affecting humans and animals and caused by an infectious misfolded protein known as prion. Among prion diseases, scrapie is the one affecting sheep and goats, and its classical form is typically acquired. In the present work, a 16S rRNA-based microbiome profiling was performed in faecal samples from 10 sheep infected with classical scrapie and 10 control sheep. The phyla Firmicutes and Bacteroidetes appeared as the most abundant phyla in scrapie and control sheep. Moreover, both groups of samples showed similar richness and alpha diversity indices. The gut microbiota profile in terms of beta diversity was significantly different in scrapie-infected sheep compared to the control group. Additionally, similarly to other neurodegenerative diseases, scrapie animals displayed a significant increased abundance of Cyanobacteria and Lentisphaerae phyla. Our results point to an altered gut microbiota in sheep infected with classical scrapie, with a specific increase of two phyla that could be involved in scrapie disease pathogenesis, enabling conceptual advances in the understanding of prion diseases. Idioma: Inglés DOI: 10.1016/j.rvsc.2025.105916 Año: 2025 Publicado en: RESEARCH IN VETERINARY SCIENCE 196 (2025), 105916 [9 pp.] ISSN: 0034-5288 Financiación: info:eu-repo/grantAgreement/ES/DGA/A19-20R Financiación: info:eu-repo/grantAgreement/ES/DGA/A20-23R Financiación: info:eu-repo/grantAgreement/ES/NextGenerationEU/INVESTIGO-100-76 Tipo y forma: Article (Published version) Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.) Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.) Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)