From Diet to Dysbiosis: The Microbiome's Relationship to Eosinophilic Esophagitis

Eosinophilic esophagitis is a chronic, type 2 inflammatory disease of the esophagus. Diet elimination trials suggest that EoE is triggered by food antigens, however, incomplete response rates present gaps in our understanding. This review aims to synthesize current evidence surrounding the diet-microbiome-immune axis in EoE and propose a conceptual framework for how dietary interventions may influence disease beyond antigen elimination.

Many studies on the EoE microbiome highlight descriptive differences in cross-sectional cohorts, although findings remain inconsistent and lack a unifying disease signature. We highlight evidence from broader mucosal and gastrointestinal microbiome research and discuss the importance of microbial metabolic function and their role in regulating epithelial barrier integrity and immune responses. We present the case that in EoE, elimination diets may unintentionally alter microbial substrates and metabolic activity, leading to heterogeneity in treatment response independent of dietary antigen removal. We review early and limited experimental data that suggest microbial metabolites such as short-chain fatty acids may influence esophageal barrier function and identify gaps in understanding mechanistic and longitudinal implications for patients. The interactions and implications of the diet-microbiome-immune axis is ripe for exploration. We explore reframing elimination diets to think beyond the antigens being removed, and probe what microbially active foods may be introduced (or not) and thus have clinically relevant microbiome-modulating properties. Future work should prioritize longitudinal, diet-controlled, and multi-omic approaches to elucidate causal relationships and support the development of microbiome-informed, precision dietary strategies in EoE.