Reduced vagus nerve activity would impact the CAP and could lead to elevated proinflammatory factors (e.g, TNFα, which is high in IBD patients) and conversely VNS of a suboptimally stimulated system could restore downstream pathways in the CAP, such as reducing TNFα release from macrophages systemically or from gut resident macrophages (Fig. 1). This evidence concerns the gene TNF and irritable bowel syndrome.