Gut instincts: Multi-level control and neural pathways involved in gastrointestinal interoception

Interoception is the process by which the nervous system senses and regulates the body's internal state to maintain homeostasis. Interoceptive processes in the gastrointestinal tract are carried out by multiple levels of sensory-motor control that are organized into hierarchical neural circuits, with different levels of command being engaged under various circumstances. The enteric nervous system provides local intrinsic control, initiating and sustaining functions like peristalsis and secretory reflexes. To coordinate motility and secretions across distant regions of the gut, the ENS recruits postganglionic neurons in prevertebral ganglia through intestinofugal sensory input. For higher control, the central nervous system becomes engaged via vagal and spinal pathways, which exhibit functional segregation for parallel processing of information. Vagal pathways regulate feeding behavior and metabolism, while lumbosacral (LS) spinal pathways are key for the conscious, voluntary control of defecation. Conversely, the thoracolumbar (TL) spinal pathways appear to serve as an 'alert system,' becoming engaged during inflammation, infection, or chronic stress and contributing to visceral pain and pathological hypersensitivity. Emerging research confirms that individual neural pathways express distinct receptors, respond to different sensory modalities, target unique CNS regions, and drive different motor and behavioral responses. By synthesizing key findings from foundational studies with results from more recent reports using modern approaches, this review aims to dissect the neural pathways of the gut-brain axis, detail their physiological roles in interoception, and explore how their dysfunction relates to visceral hypersensitivity, pathological interoceptive awareness, and other GI-related symptoms.