Brain-gut-spleen axis (BGSA)

The brain-gut-spleen axis is a complex bidirectional communication network that integrates the central nervous system, the gastrointestinal tract, and the immune system to maintain systemic homeostasis (Teratani et al., 2020, Nature). This axis primarily operates through the vagus nerve and the hypothalamic-pituitary-adrenal (HPA) axis, which transmit signals from the brain and gut to the spleen, a critical site for the regulation of systemic immunity (Bronte & Pittet, 2013, Immunity). A central component of this signaling is the "cholinergic anti-inflammatory pathway," where neural impulses in the vagus nerve trigger the release of acetylcholine in the spleen, which then binds to alpha-7 nicotinic acetylcholine receptors on macrophages to inhibit the production of pro-inflammatory cytokines like TNF-alpha (Pavlov & Tracey, 2012, Nature Reviews Endocrinology). Dysregulation of the brain-gut-spleen axis is implicated in the pathogenesis of various conditions, including inflammatory bowel disease, rheumatoid arthritis, sepsis, and certain neuropsychiatric disorders (Ji et al., 2014, Scientific Reports). While the axis itself is a physiological system rather than a single molecular target, therapeutic strategies such as bioelectronic vagus nerve stimulation and pharmacological modulation of neuroendocrine receptors are being explored to treat chronic inflammatory and autoimmune diseases (Koopman et al., 2016, PNAS).

Other names

Brain-gut-immune axisNeuro-immune-endocrine axisVagus-splenic nerve axisBrain-gut-microbiota-immune axis

Modulation of the cholinergic anti-inflammatory pathway via vagal efferents and the hypothalamic-pituitary-adrenal (HPA) axis to regulate splenic cytokine production and systemic immune homeostasis.