The vagus nerve (VN), a key component of the parasympathetic nervous system, plays a critical role in the microbiota-gut-brain axis. It is a mixed nerve with 80% afferent and 20% efferent fibers, capable of sensing gut microbiota metabolites and transmitting signals to the central nervous system (CNS), where they are integrated into the central autonomic network (CAN). The VN also participates in the cholinergic anti-inflammatory pathway, which helps dampen inflammation and reduce intestinal permeability, thereby modulating microbiota composition. Stress reduces VN activity, leading to increased gut inflammation and dysbiosis, which are associated with conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). A low vagal tone is observed in these patients, contributing to chronic inflammation. Targeting the VN, such as through vagus nerve stimulation (VNS), has potential therapeutic applications in restoring homeostasis in the microbiota-gut-brain axis. VNS has been shown to reduce intestinal inflammation and permeability, and may be beneficial in treating IBS and IBD. The VN also communicates with the gut through enteroendocrine cells (EECs), which release neurotransmitters and hormones that influence gut function. These cells detect microbial products and communicate with the VN, which then transmits signals to the CNS. The VN's role in the microbiota-gut-brain axis is further supported by studies showing that microbial products like short-chain fatty acids (SCFAs) can activate VN afferent fibers. The VN also interacts with the immune system, modulating macrophage activity and inflammation. Stress and psychological factors can influence the VN and gut microbiota, highlighting the complex interplay between the gut, brain, and immune system. Overall, the VN is a critical mediator in the microbiota-gut-brain axis, and its modulation through VNS or other interventions may offer new therapeutic strategies for gastrointestinal and neurological disorders.The vagus nerve (VN), a key component of the parasympathetic nervous system, plays a critical role in the microbiota-gut-brain axis. It is a mixed nerve with 80% afferent and 20% efferent fibers, capable of sensing gut microbiota metabolites and transmitting signals to the central nervous system (CNS), where they are integrated into the central autonomic network (CAN). The VN also participates in the cholinergic anti-inflammatory pathway, which helps dampen inflammation and reduce intestinal permeability, thereby modulating microbiota composition. Stress reduces VN activity, leading to increased gut inflammation and dysbiosis, which are associated with conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). A low vagal tone is observed in these patients, contributing to chronic inflammation. Targeting the VN, such as through vagus nerve stimulation (VNS), has potential therapeutic applications in restoring homeostasis in the microbiota-gut-brain axis. VNS has been shown to reduce intestinal inflammation and permeability, and may be beneficial in treating IBS and IBD. The VN also communicates with the gut through enteroendocrine cells (EECs), which release neurotransmitters and hormones that influence gut function. These cells detect microbial products and communicate with the VN, which then transmits signals to the CNS. The VN's role in the microbiota-gut-brain axis is further supported by studies showing that microbial products like short-chain fatty acids (SCFAs) can activate VN afferent fibers. The VN also interacts with the immune system, modulating macrophage activity and inflammation. Stress and psychological factors can influence the VN and gut microbiota, highlighting the complex interplay between the gut, brain, and immune system. Overall, the VN is a critical mediator in the microbiota-gut-brain axis, and its modulation through VNS or other interventions may offer new therapeutic strategies for gastrointestinal and neurological disorders.