Gut Fungi in Alzheimer's Disease: Mechanisms, Biomarkers and Therapeutic Potential.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of aging that imposes a heavy medical and socioeconomic burden. Its multifactorial pathology-including amyloid-β (Aβ) accumulation, tauopathy, and chronic neuroinflammation-lacks effective disease-modifying treatments. Recent studies highlight the gut-brain axis, specifically the intestinal mycobiome (fungal community), as a novel factor in AD. In this review, we summarize evidence on gut fungi in AD. Altered gut fungal profiles have been reported in AD patients, including enrichment of Candida tropicalis and Schizophyllum commune and reduction of Rhodotorula mucilaginosa, and in AD mouse models, such as increased abundance of the Dipodascaceae family. Fungi can translocate or release bioactive molecules that impact the brain; for instance, fungal proteins (enolase, β-tubulin) and polysaccharides (chitin) have been detected in AD brain tissue. Fungal metabolites also emerge as potential biomarkers; notably, plasma sterigmatocystin levels were significantly higher in AD patients compared to controls. Mechanistically, gut fungi (such as Candida or Malassezia species) may activate microglia and promote Aβ deposition via inflammatory pathways, while fungal prion-like proteins can accelerate AD protein aggregation in vitro. Conversely, certain fungi exert neuroprotective effects; oral administration of the probiotic yeast Saccharomyces boulardii attenuated cognitive deficits and Aβ pathology in APP/PS1 mice. Importantly, fecal fungal profiling is non-invasive and may serve as a practical AD screening tool. Collectively, these findings nominate gut fungi as potential biomarkers and therapeutic targets. Future work should validate specific mycobiome signatures and develop fungus-targeted interventions to enable earlier diagnosis and novel treatments for AD.