Abstract

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic 
lateral sclerosis represent a growing global health challenge, with complex etiologies that remain incompletely 
understood. Emerging evidence highlights the critical role of the gut microbiome in modulating 
neuroinflammation, immune responses, and neuronal function through the gut–brain axis. Alterations in microbial 
diversity and metabolite production have been linked to disease onset, progression, and symptom severity, 
suggesting that host–microbe interactions are integral to neurodegenerative pathology. Advances in sequencing 
technologies and multi-omics approaches are unraveling these mechanisms, while therapeutic strategies, including 
probiotics, prebiotics, synbiotics, dietary interventions, and fecal microbiota transplantation are being investigated 
for their potential to restore microbial balance and improve clinical outcomes. Despite these promising insights, 
major challenges remain, including disentangling causality from correlation, addressing methodological 
variability, and ensuring ethical and regulatory oversight in clinical applications. This review synthesizes current 
knowledge of gut microbiome–neurodegeneration interactions, evaluates therapeutic opportunities, and highlights 
future directions for research, precision medicine, and public health.