BACKGROUND: Chronic insomnia disorder (CID) is a widespread sleep disorder linked to increased risks of various chronic diseases and often precedes neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Emerging evidence suggests that gut microbiome disturbances contribute to CID through the gut-brain axis, involving microbial metabolites and neuroactive proteins.
OBJECTIVES: This study explored the relationships between serum 1,3-β-D-glucan (a marker of intestinal permeability and microbial translocation), alpha-synuclein (αSyn, a neuronal protein implicated in neurodegeneration), and sleep architecture in chronic insomnia individuals compared to healthy controls.
METHODS: Blood samples were taken from 15 people who had been diagnosed with CID, based on their results from the Pittsburgh Sleep Quality Index (PSQI) and video-polysomnography tests. For comparison, blood was also collected from 15 healthy volunteers, whose sleep quality was assessed using the PSQI. Serum concentrations of 1,3-β-D-glucan and αSyn protein were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS: The findings showed significantly elevated serum 1,3-β-D-glucan (p < 0.0001) and αSyn (p < 0.001) levels in the CID group, with a strong positive correlation between these markers (r = 0.964, p < 0.01). Moreover, increased αSyn levels were associated with alterations in sleep stages, particularly prolonged rapid eye movement (REM) sleep duration (r = 0.560, p < 0.05).
CONCLUSIONS: These findings support a mechanistic link between gut microbiota disruption, αSyn pathology, and altered sleep architecture in CID, highlighting novel pathways for understanding the neuroimmune mechanisms underlying sleep disturbances. Serum 1,3-β-D-glucan and αSyn may serve as potential biomarkers for identifying insomniac individuals at risk of synucleinopathies and offer novel targets for therapeutic intervention aimed at restoring gut health and improving sleep quality.