Maria CIUBOTARU, Alin Stelian CIOBICA
ABSTRACT :
Neurodegenerative diseases (NDs), which include Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies (DLB), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are a major and growing global health burden caused primarily by population aging and a lack of effective diseasemodifying therapies. A significant restriction in contemporary clinical practice is the lack of accurate biomarkers capable of detecting disease during the preclinical or prodromal stages, when therapeutic interventions may be most successful. Increasing evidence from clinical, epidemiological, and experimental investigations suggests that changes in the gut microbiome precede overt neurological symptoms and contribute to neurodegenerative processes via the microbiota-gut-brain axis. This axis connects neuronal, immunological, endocrine, and metabolic signaling pathways, allowing intestinal bacteria to impact neuroinflammation, bloodbrain barrier integrity, microglial activation, and protein aggregation in the central nervous system. This article summarizes evidence from human cohort studies and animal models demonstrating gut microbiome dysbiosis in major neurodegenerative diseases, discusses mechanistic pathways linking intestinal microbiome to neurodegeneration, and assesses the utility of microbiomederived signatures as non-invasive biomarkers for early and differential diagnosis. Finally, the methodological obstacles and future research approaches necessary for clinical translation are discussed. Keywords: Neurodegenerative diseases; Microbiota–Gut– Brain Axis; Early diagnosis.