Diet–Microbiome–Immune Interactions at the Gut Mucosa in Food Allergy: Mechanisms, Gaps, and Therapeutic Implications

Mucosal surfaces are sites of highly dynamic interactions among epithelial and immune cells, environmental exposures, particularly dietary inputs, and the diverse microbial communities and their metabolites. These elements continually influence each other to maintain homeostasis and ensure appropriate immune discrimination between pathogens and innocuous stimuli, such as commensal microbes and dietary antigens. When this balance is disrupted, immune tolerance breaks down, leading to maladaptive responses characteristic of food allergy. Targeting mucosal interactions to restore homeostasis, therefore, holds substantial promise for preventing and treating food allergies and other atopic diseases. However, the complexity of the interconnected networks linking host factors, the microbiome, and diet presents major challenges. In this review, we synthesize recent advances in understanding the mechanisms governing mucosal crosstalk in both health and allergic disease. We provide an in-depth examination of the intestinal mucus layer and its components as active mediators of microbiota-host communication and potential initiators of allergic responses. We also discuss emerging mechanistic and therapeutic insights into how diet, food-derived molecules or treatments shape mucosal immunity, and highlight key knowledge gaps that warrant further investigation to clarify how disruptions in these interactions contribute to allergic sensitization.