Role of physical exercise, vagal nerve stimulation, and vagotomy in inflammatory bowel disease

Table 1 Comparative effects of physical exercise, vagal nerve stimulation, and vagotomy on inflammatory bowel disease

Evaluated aspect	Physical exercise	Vagal nerve stimulation	Vagotomy
Vagal tone	Increases vagal tone	Directly stimulates the vagus nerve	Interrupts vagal modulation
Inflammatory cytokines	Reduces TNF-α, IL-6, IL-1β via myokines	Inhibits TNF-α, IL-6, IL-1β through cholinergic anti-inflammatory pathway	Increases TNF-α, IL-6, and other pro-inflammatory cytokines
Myokines/protective mediators	Increases IL-6 (anti-inflammatory action), IL-10, IL-1ra, irisin
Intestinal barrier integrity	Improves the mucosal barrier	Enhances tight junction proteins (occludin, ZO-1), protects the barrier	Reduces barrier integrity
Gut microbiota	Increases diversity, short-chain fatty acid production	Positively modulates microbiota	May worsen dysbiosis
Neurotransmitters/gut-brain axis	Increases serotonin, dopamine, endorphins, improves mood and brain-gut communication	Modulates the brain-gut axis via central vagal projections	Disrupts autonomic and central regulation
Overall inflammation in IBD	Decreases inflammation and symptoms	Reduces inflammation, may promote remission	Exacerbates intestinal inflammation
Stress response/HPA axis	Reduces cortisol and oxidative stress	Regulates HPA axis through vagal signaling	Impairs HPA axis regulation
Immune modulation	Improves intestinal immune function	Modulates immune cells via α7nAChR (e.g., macrophages, Tregs)	Weakens immune response
Application method	Non-invasive, safe	Invasive (implant) or non-invasive (auricular/cervical transcutaneous)	Surgical, irreversible
Risks/side effects	Gastrointestinal symptoms with excessive intensity (nausea, cramps)	Invasive vagal nerve stimulation may cause dysphonia, pain, infection; non-invasive is well tolerated	Increases IBD risk; worsens inflammation in animal models
Current clinical use in IBD	Complementary (recommended: Light/moderate aerobic activity)	Emerging therapy with promising results in Crohn’s disease and ulcerative colitis	Not recommended; associated with worsened outcomes

IBD: Inflammatory bowel disease; HPA: Hypothalamic-pituitary-adrenal; TNF-α: Tumor necrosis factor α; IL-6: Interleukin-6; IL-1β: Interleukin-1β; IL-10: Interleukin-10; IL-1ra: Interleukin-1 receptor antagonist; ZO-1: Zonula occludens-1; Tregs: Regulatory T cells; α7nAChR: Alpha-7 nicotinic acetylcholine receptor.