Enteric nervous system and vagus nerve pathway (ENS-VN pathway)

The enteric nervous system (ENS) and vagus nerve pathway constitute the fundamental neural architecture of the gut-brain axis, enabling continuous bidirectional communication between the gastrointestinal tract and the brain (Furness, 2012). The ENS, often referred to as the "second brain," consists of millions of neurons organized into the myenteric and submucosal plexuses that autonomously regulate digestion, while the vagus nerve serves as the primary conduit for visceral sensory (afferent) and parasympathetic motor (efferent) signals (Breit et al., 2018). This pathway is critical for physiological processes such as nutrient sensing, gastric emptying, and the regulation of systemic inflammation through the cholinergic anti-inflammatory reflex (Pavlov & Tracey, 2012). Pathological changes in this circuit are linked to a wide range of disorders, including irritable bowel syndrome (IBS), gastroparesis, and obesity, as well as the early stages of Parkinson's disease, where alpha-synuclein pathology may travel from the gut to the brain via the vagus nerve (Braak et al., 2003). Therapeutic strategies include the use of GLP-1 receptor agonists to stimulate vagal satiety signals and 5-HT4 receptor agonists to enhance enteric neurotransmission, alongside non-pharmacological approaches like vagus nerve stimulation (VNS) for treating epilepsy and depression (Krieger, 2020).

Other names

Gut-brain axisVagal afferent pathwayEnteric-vagal circuitMicrobiota-gut-brain axisVagal-enteric signaling

Modulation of neural signaling through the activation or inhibition of specific receptors (e.g., 5-HT4, GLP-1R) on enteric neurons or vagal afferent fibers to alter gastrointestinal function and central feedback (Krieger, 2020; Furness, 2012).