Gut–brain communication: types of sensory nerves and mechanisms of activation

Understanding the locations of extrinsic sensory nerve endings in the gastrointestinal tract and their mechanisms of activation is essential to advancing our understanding of how communication along the gut–brain axis affects health and disease. The gastrointestinal tract detects diverse stimuli (chemical, mechanical and thermal signals) via two major types of primary afferent (sensory) nerves: vagal and spinal afferents. Viscerofugal neurons represent a third pathway that has been indirectly implicated in gut–brain signalling. These spinal and vagal afferents transmit sensory signals to the brain through distinct pathways, and although the origins of their nerve cell bodies are known, their nerve endings remain poorly understood. New evidence indicates that single dorsal root ganglia neurons can give rise to multiple different morphological types of endings within different gut layers, and that Piezo2 channels have a major role in detecting mechanosensory stimuli by gut-projecting spinal afferents. Morphological studies suggest that substances released from enteroendocrine cells can activate the terminals of vagal and spinal afferent endings within the mucosa through a paracrine mechanism. Here, we review the distinct spinal and vagal afferent types alongside viscerofugal pathways revealed by advances in neurogenetic techniques and high-resolution anterograde tracing, linking them to their physiological role in gut–brain communication.