The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis

Abstract

The microbiota, the gut, and the brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (VN), the principal component of the parasympathetic nervous system, is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN, because of its role in interoceptive awareness, is able to sense the microbiota metabolites through its afferents, to transfer this gut information to the central nervous system where it is integrated in the central autonomic network, and then to generate an adapted or inappropriate response. A cholinergic anti-inflammatory pathway has been described through VN's fibers, which is able to dampen peripheral inflammation and to decrease intestinal permeability, thus very probably modulating microbiota composition. Stress inhibits the VN and has deleterious effects on the gastrointestinal tract and on the microbiota, and is involved in the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) which are both characterized by a dysbiosis. A low vagal tone has been described in IBD and IBS patients thus favoring peripheral inflammation. Targeting the VN, for example through VN stimulation which has anti-inflammatory properties, would be of interest to restore homeostasis in the microbiota-gut-brain axis.

Keywords: cholinergic anti-inflammatory pathway; microbiota-gut-brain axis; stress; vagus nerve; vagus nerve stimulation.

Figure 1

Communication between the central nervous system and the microbiota through the vagus nerve (VN). VN afferent fibers can be stimulated by microbiota components either directly or indirectly via gut endocrine cells (GEC). VN afferent fibers exert stimuli on the central nervous system via the central autonomic network (CAN). VN afferent fibers are able to stimulate efferent fibers through the inflammatory reflex. VN efferent fibers can reduce digestive inflammation and reduce intestinal permeability by tight junction reinforcement. These actions of vagal efferent fibers can indirectly modulate microbiota composition. Alongside with brain-VN-microbiota axis exists bi-directional communication by various ways.

Figure 2

Vagal terminal afferent endings. Antral gland afferent endings begin to divide at the level of the muscularis mucosae, and surrond gastric antral glands creating arbors. Villus afferent endings divide at the basal pole of the crypts, and ramify repeatedly at the apical half of the villus. Crypt afferent endings divide at the basal pole of the crypts, and collaterals encircle multiple time the crypts or the intestinal glands.