Persistent Diet–Microbiome–Epithelial Abnormalities Continue During Crohn’s Disease Remission : Gastroenterology | May 2026

Introduction

Modern biologic therapies have significantly improved remission rates in Crohn’s disease (CD), primarily through suppression of mucosal immune activation. However, despite clinical and endoscopic remission, many patients continue to experience recurrent disease flares, suggesting that deeper pathogenic mechanisms may persist even under effective immune-targeted treatment.

Problem Statement

Current treatment paradigms in CD focus heavily on immune suppression, yet little is known about the residual dietary, microbial, metabolic and epithelial abnormalities that remain during remission. Understanding these persistent nonimmune perturbations may explain the relapsing nature of CD and identify adjunct therapeutic targets beyond biologic therapy alone.

Summary

This comprehensive multiomics study demonstrates that substantial abnormalities in diet, gut microbiota, metabolome and ileal epithelial biology persist in Crohn’s disease despite effective clinical remission and advanced biologic therapy. Patients in remission showed marked suppression of adaptive T-cell and innate granulocyte pathways, reflecting strong immune inhibition, yet simultaneously exhibited persistent activation of epithelial antibacterial pathways including DUOX2, CEACAM6 and REG family genes. Increased goblet-cell and mucin glycosylation signatures were also observed, potentially representing a compensatory epithelial response to ongoing microbial disruption. Importantly, remission was still characterized by persistent dysbiosis, reduced microbial diversity and metabolomic abnormalities similar to those observed in active disease. Dietary analysis revealed sustained unhealthy dietary patterns during remission, particularly higher intake of ultra processed foods and lower consumption of fiber, vegetables and micronutrients. Exposure to ultra processed foods correlated strongly with microbial dysbiosis and negatively correlated with genes involved in mucin glycosylation and epithelial barrier maintenance, whereas Mediterranean dietary adherence showed favorable associations. Notably, higher epithelial antibacterial and mucus-related signatures, greater dysbiosis and increased ultra processed food exposure were associated with subsequent clinical flare risk. Overall, the study supports a major conceptual shift in CD management by demonstrating that immune suppression alone may not fully normalize gut biology and that adjunctive strategies targeting the diet–epithelium–microbiome axis could be essential for achieving deeper and more durable remission states.