Gut Microbiota-Immune System Interactions in Health and Neurodegenerative Diseases: Insights into Molecular Mechanisms and Therapeutic Applications.

The human body contains approximately 100 trillion microorganisms, predominantly within the gastrointestinal tract, collectively called the gut microbiota. Investigations have revealed the bidirectional communication between the gut microbiota and the brain, characterized as the "microbiota-gut-brain axis." This axis represents an important regulator of brain development and function, immune system development, and nutrient metabolism, making it a target for efforts to alleviate the development and progression of neurodegenerative diseases (NDDs). Despite extensive biomedical and clinical research, our understanding of the causes, optimal treatment, and progression of NDDs remains limited. This paper aims to summarize the available knowledge on the role played by gut microbiota and how it is connected to the progression of neurodegenerative conditions; in particular, the relationship between the microbiota and gut-brain communications and the gut microbiota and neuro-immune conditions is reviewed. We discuss how and why the gut immune system communicates with the brain and how this communication impacts neurodegeneration. Next, we examine the alterations in the gut microbiota, immune response, and brain changes associated with gut dysbiosis. Finally, we highlight the preclinical and clinical evidence for probiotics, prebiotics, fecal microbiota transplantation, dietary supplements, natural drugs, and exercise intervention as potential therapeutic approaches that could lead to a new treatment paradigm for NDDs.