The Vagus Nerve in the Neuro-Immune Axis: Implications in the Pathology of the Gastrointestinal Tract

Abstract

The vagus nerve (VN) is the longest nerve of the organism and a major component of the parasympathetic nervous system which constitutes the autonomic nervous system (ANS), with the sympathetic nervous system. There is classically an equilibrium between the sympathetic and parasympathetic nervous systems which is responsible for the maintenance of homeostasis. An imbalance of the ANS is observed in various pathologic conditions. The VN, a mixed nerve with 4/5 afferent and 1/5 efferent fibers, is a key component of the neuro-immune and brain-gut axes through a bidirectional communication between the brain and the gastrointestinal (GI) tract. A dual anti-inflammatory role of the VN is observed using either vagal afferents, targeting the hypothalamic–pituitary–adrenal axis, or vagal efferents, targeting the cholinergic anti-inflammatory pathway. The sympathetic nervous system and the VN act in synergy, through the splenic nerve, to inhibit the release of tumor necrosis factor-alpha (TNFα) by macrophages of the peripheral tissues and the spleen. Because of its anti-inflammatory effect, the VN is a therapeutic target in the treatment of chronic inflammatory disorders where TNFα is a key component. In this review, we will focus on the anti-inflammatory role of the VN in inflammatory bowel diseases (IBD). The anti-inflammatory properties of the VN could be targeted pharmacologically, with enteral nutrition, by VN stimulation (VNS), with complementary medicines or by physical exercise. VNS is one of the alternative treatments for drug resistant epilepsy and depression and one might think that VNS could be used as a non-drug therapy to treat inflammatory disorders of the GI tract, such as IBD, irritable bowel syndrome, and postoperative ileus, which are all characterized by a blunted autonomic balance with a decreased vagal tone.

Exercise activates vagal induction of dopamine and attenuates systemic inflammation

“…These results concur with previous studies showing that vagal stimulation can attenuate TNF production in arthritis (Bassi et al, 2017; Koopman et al, 2016), ischemia/reperfusion (Altavilla et al, 2006; Bernik et al, 2002; Cai et al, 2009), hemorrhage/resuscitation (Cai et al, 2009; de Souza et al, 2010), post-operative recovery (Grech et al, 2016), pancreatitis (Van Westerloo et al, 2006), endotoxemia (Borovikova et al, 2000; Deitch and Ulloa, 2010; Huston et al, 2006b) and severe sepsis (Ulloa, 2011; van Westerloo et al, 2005; Wang et al, 2004). Our results also concur with previous studies showing that exercise increased the vagal cardiovascular tone (Bonaz et al, 2017; Carnevali and Sgoifo, 2014; Ulloa et al, 1998). But, other study reported that exercise modulates cardiovascular but not through the vagus nerve (Neto et al, 2017).…”

“…4b). Given that exercise can increase the vagal tone (Bonaz et al, 2017; Carnevali and Sgoifo, 2014) and that the vagus nerve can inhibit splenic TNF production (Borovikova et al, 2000; Huston et al, 2006a; Huston et al, 2006b), we analyzed whether the vagus nerve contributes to the effects of exercise. Unilateral right cervical vagotomy did not prevent the anti-inflammatory potential of exercise (Fig.…”

“…Then, exercise attenuated serum TNF levels in sham but not in splenectomized mice. Given that previous studies reported that exercise can increase the vagal tone (Bonaz et al, 2017; Carnevali and Sgoifo, 2014) and that vagal stimulation can inhibit splenic TNF production (Borovikova et al, 2000; Huston et al, 2006a; Huston et al, 2006b), we analyzed the role of the vagus nerve in exercise control of inflammation. Both, cervical or subdiaphragmatic vagotomy prevented exercise control of serum TNF levels, showing that exercise control of inflammation is mediated by the vagus nerve.…”

Exercising the hepatobiliary‐gut axis. The impact of physical activity performance

“…Gut microbiota interacts with BAs in the enterohepatic circulation by converting primary to secondary BAs which, in turn, regulate microbiota by exerting antimicrobial effects. 189 This scenario might also involve a neurohormonal mechanism with vagal-mediated gallbladder emptying before exercise. 185 Regular physical activity also leads to increased vagal tone 186,187 and decreased expression of inflammatory markers, 187 although recent studies provide conflicting results or suggest reduction in circulatory apoptosis marker 112,188 , an effect correlating with high cardiorespiratory fitness.…”

GHSR‐1 agonist sensitizes rat colonic intrinsic and extrinsic neurons to exendin‐4: A role in the manifestation of postprandial gastrointestinal symptoms in irritable bowel syndrome?

“…Unlike healthy controls, patients with IBS appear to be conscious of these sensory inputs, which is interpreted as abdominal discomfort or pain. The vagus nerve has been linked to activation of the hypothalamic‐pituitary stress axis, and modification of gut‐originating pain signaling, which, in turn, leads to altered gut function . The entire GI tract in rats is innervated by the vagus, and the dorsal motor nucleus of the vagus and vagal afferents are sensitive to GLP‐1 .…”