The Enteric Nervous System: A Controller of Gut Barrier and Allergy Risk

The enteric nervous system (ENS) controls intestinal barrier integrity and is directly linked to allergy susceptibility. For allergists and immunologists, this matters because impaired barrier function facilitates antigen translocation and immune sensitization. Clinically, assessing ENS-mediated barrier control adds a relevant dimension to allergy risk evaluation.

Neuronal release of vasoactive intestinal peptide (VIP) regulates LGR5+ intestinal stem cell proliferation and differentiation, shaping epithelial renewal and baseline permeability. By restraining excess differentiation toward secretory tuft cells—cells that can promote type 2–skewed mucosal responses—the VIP→stem cell axis provides a plausible mechanism linking neuronal signaling to barrier integrity.

Loss of ENS signaling or reduced VIP activity increases epithelial permeability, permitting greater allergen translocation and amplifying mucosal type 2 inflammatory responses. That dysregulation can raise allergy susceptibility and contribute to chronic gut disorders characterized by sustained immune activation, underscoring clear implications for both allergic sensitization and chronic intestinal inflammation.

Dietary measures that support mucosal health—fermentable fiber and select prebiotics or probiotic strains that favor mucosal metabolites—could bolster epithelial renewal and neuronal signaling. These interventions remain mechanistically plausible but lack direct evidence as targeted modulators of the ENS–VIP axis; targeted clinical trials are needed to test dietary strategies that support the nerve–gut axis.

For clinicians, these data shift attention to neuroimmune contributors when evaluating barrier-related allergy risk. Translation pathways include biomarker development (for example, measures of epithelial turnover or readouts of VIP pathway activity) and exploration of therapeutic approaches to modulate VIP signaling.