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

Figure 1 This illustration shows activation of the vagal cholinergic anti-inflammatory pathway in response to intestinal inflammation, as observed in inflammatory bowel diseases such as Crohn’s disease. On the left, the anatomical connection between the brain, vagus nerve, and gastrointestinal tract is shown. The enlarged section on the right illustrates an inflamed intestinal mucosa, characterized by microbiota dysbiosis (1), disruption of the epithelial barrier, and immune cell infiltration (2). Vagal efferent fibers release acetylcholine, which binds to the alpha-7 nicotinic acetylcholine receptor expressed on macrophages and dendritic cells (3). This binding suppresses the differentiation of T helper 17 cells (pro-inflammatory helper T lymphocytes) that produce interleukin (IL)-17 and IL-22 (4), inhibits the release of pro-inflammatory cytokines (tumor necrosis factor α, IL-1, IL-8, high mobility group box 1) (5), while promoting the expansion of forkhead box protein 3+ regulatory T cells (6), contributing to immune homeostasis. α7nAChR: Alpha-7 nicotinic acetylcholine receptor; Th17: T helper 17 cells; FoxP3+ Treg: Regulatory T cells expressing the transcription factor forkhead box protein 3; TNF-α: Tumor necrosis factor α; IL-1: Interleukin-1; IL-8: Interleukin-8; HMGB-1: High mobility group box 1; IL-17: Interleukin-17; IL-22: Interleukin-22.

Figure 2 Schematic representation of the modulatory effects on intestinal inflammation by three different interventions: Physical exercise (left), vagus nerve stimulation (lower right), and subdiaphragmatic vagotomy (upper right). Physical exercise and vagus nerve stimulation promote protective effects through increased vagal tone and activation of the cholinergic anti-inflammatory pathway. In contrast, vagotomy disrupts this pathway, leading to reduced protective effects and potential exacerbation of intestinal inflammation. IBD: Inflammatory bowel disease; GI: Gastrointestinal.