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

Area of Science:

• Neuroscience
• Microbiology
• Gastroenterology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex pathology and limited treatments.
• The gut-brain axis, including the intestinal mycobiome (fungal community), is a novel area of AD research.
• Current understanding of the gut mycobiome's role in AD pathogenesis and potential as biomarkers is evolving.

Purpose of the Study:

• To review current evidence on the role of gut fungi in Alzheimer's disease.
• To explore the potential of gut fungi as diagnostic biomarkers and therapeutic targets for AD.
• To highlight the implications of fungal presence and metabolites in AD brain pathology.

Main Methods:

• Review of existing literature on gut mycobiome alterations in AD patients and models.
• Analysis of studies investigating fungal components and metabolites in AD brain tissue and biofluids.
• Examination of research on the mechanistic links between gut fungi and AD pathology (neuroinflammation, protein aggregation).

Main Results:

• Altered gut fungal profiles (e.g., increased Candida tropicalis, decreased Rhodotorula mucilaginosa) observed in AD patients and models.
• Fungal components (enolase, chitin) and metabolites (sterigmatocystin) detected in AD brain tissue and elevated in AD patient plasma.
• Mechanisms include fungal activation of microglia, promotion of amyloid-β (Aβ) deposition, and acceleration of protein aggregation.
• Probiotic yeast Saccharomyces boulardii showed neuroprotective effects in AD mouse models.

Conclusions:

• Gut fungi represent potential non-invasive biomarkers for AD screening and diagnosis.
• Fungal metabolites and specific fungal signatures warrant further investigation as AD biomarkers.
• Targeting gut fungi offers novel therapeutic strategies for Alzheimer's disease.
• Fecal fungal profiling presents a practical approach for early AD detection.