BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.

Biomedical Research Center University Hospital of Hradec Králové 500 05 Hradec Králové Czech Republic

College of Humanities and New Media Yangtze University Jingzhou 434025 China

College of Life Science Yangtze University Jingzhou 434025 China

College of Physical Education and Health Chongqing College of International Business and Economics Chongqing 401520 China

Department of Chemistry Faculty of Science University of Hradec Králové 500 03 Hradec Králové Czech Republic

School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou 310024 China

State Key Laboratory for Managing Biotic and Chemical Threats to The Quality and Safety of Agro Products Key Laboratory of Traceability for Agricultural Genetically Modified Organisms Ministry of Agriculture and Rural Affairs Zhejiang Academy of Agricultural Sciences Hangzhou 310021 China

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