The gut neuroepithelial unit as a neurodegeneration-relevant interface in the gut–brain axis

Abstract Neurodegenerative diseases are increasingly linked to abnormalities in the gut–brain axis, yet the local intestinal interface at which luminal and mucosal perturbations are related with the central nervous system remains poorly defined. The gut neuroepithelial unit (GNU) is proposed as a localized mucosal signalling interface composed of sensory epithelial cells, enteric neurons, glia and adjacent immune-stromal elements that detect, encode and route intestinal information into neural, endocrine and immune outputs. This framework shifts the intestine from being a diffuse upstream modifier of brain pathology to a mesoscopic unit through which microbial products, barrier dysfunction, inflammatory cues and metabolic signals are transformed into disease-relevant gut-to-brain communication. Particularly, in Parkinson’s disease and Alzheimer’s disease, the GNU may function as a conditional interface that amplifies, filters or biases peripheral signals before they engage central circuits. The GNU therefore provides a tractable framework for mechanistic dissection, translational stratification and peripheral therapeutic targeting in neurodegeneration.