Vagus nerve and brain-gut communication in neurodegenerative diseases: Mechanism and therapeutic perspectives

Neurodegenerative diseases (NDs) are characterized by degenerative nerve damage, and available therapeutic drugs cannot prevent or slow down their progression. The pathogenesis of NDs is related to the brain-gut axis, but the regulatory mechanisms are not yet fully understood. The vagus nerve, the main neural pathway of the brain-gut axis, plays a crucial role in the occurrence and development of NDs. This study summarizes the molecular mechanisms by which the vagus nerve regulates intestinal immunity and neuroinflammatory homeostasis of NDs to improve movement disorders and mental disorders. Intestinal immune dysregulation promotes the transfer of metabolites through the vagus nerve to the brain, leading to a general imbalance between the central immune response and the peripheral immune response and enhancing the level of systemic inflammatory stress. Intestinal immune responses and metabolic imbalances cause brain immune imbalances mediated by the vagus nerve and brain-gut communication. Targeted strategies of vagus nerve and brain-gut communication, including intelligent engineered strains systems, genetic-engineering strain modification, artificial intelligence dynamic monitoring, vagus nerve stimulation, polysaccharides, and natural small molecules, can help improve the symptoms of NDs. This study emphasizes that vagus nerve and brain-gut communication can serve as novel targets for NDs.