Alterations in Skin Microbiota in Patients with Spinocerebellar Ataxia Type 3: A Pilot Study

Spinocerebellar ataxia type 3 (SCA3) exhibits marked variability in age of onset and disease progression that cannot be fully explained by CAG repeat length, indicating the presence of additional modifiers. The skin, as a neuro-immune interface, has been linked to neurological diseases but remains understudied in SCA3. The study aimed to characterize the skin microbiota in SCA3 and assess its relationship with disease severity.

The study characterized the neck and armpit skin microbiota in 30 genetically confirmed SCA3 patients and 30 age and sex-matched healthy controls using 16S rRNA sequencing, and assessed site-specific microbial differences and their associations with clinical and genetic measures.

The neck exhibited higher alpha diversity and a distinct microbial composition compared with the armpit (P = 0.001). Microbial differences between patients and healthy controls were observed at both sites (armpit, P = 0.009; neck, P = 0.023). Relative abundances of 7 taxa were associated with motor severity, disease duration, and/or CAG repeat length, with functional predictions indicating alterations in metabolic and stress-related pathways. Site-specific microbial signatures from the neck or armpit showed diagnostic potential, achieving an AUC of 0.84 (95% CI, 0.64-1.00).

These findings suggest that the skin microbiome may represent a disease-associated signal in SCA3, warranting larger longitudinal and mechanistic studies to clarify its clinical relevance and biological significance.

SCA3 is associated with alterations in the skin microbiota. These changes are associated with disease severity and show potential for distinguishing patients from controls, supporting their possible utility as biomarkers.