Esophageal and Small Intestinal Mucosal Integrity in Eosinophilic Esophagitis and Response to an Elemental Diet

Abstract

Objectives:The esophageal mucosal integrity is impaired in eosinophilic esophagitis (EoE) and it has been suggested that the duodenal permeability is increased. The absence of food allergens may restore the integrity. The aims of this study were to assess duodenal permeability in EoE and to evaluate the effect of an elemental diet on the esophageal and duodenal integrity.Methods:In this prospective study 17 adult EoE patients and 8 healthy controls (HC) were included. Esophageal biopsy specimens were sampled before and after 4 weeks of elemental diet to measure eosinophil counts and gene expression of tight junction and barrier integrity proteins. Esophageal and duodenal impedance were measured by electrical tissue impedance spectroscopy and Ussing chambers were used to measure transepithelial resistance (TER) and transepithelial molecule flux. Small intestinal permeability was measured using a test, measuring lactulose/mannitol (L/M) ratios.Results:In EoE patients, the esophageal but not the duodenal integrity was impaired, compared with HC. We observed no significant difference between L/M ratios of HC and EoE patients. After diet, eosinophil counts decreased significantly, which was paralleled by normalization of esophageal impedance and transepithelial molecule flux. The esophageal TER improved significantly, but did not reach values seen in HC. Esophageal expression of genes encoding for barrier integrity proteins filaggrin and desmoglein-1 was impaired at baseline and restored after diet.Conclusions:An elemental diet restores esophageal integrity, suggesting that it is at least partly secondary to allergen exposure. Duodenal integrity seems not to be affected in EoE, and possibly plays a minor role in its pathophysiology.

Leaky gut: mechanisms, measurement and clinical implications in humans

“…Two separate groups independently studied small bowel permeability in patients with eosinophilic oesophagitis; one group documented increased small bowel permeability, though the mechanism whereby this results in the eosinophilic infiltration of the oesophagus is unclear57; the second group did not document increased small bowel permeability, but they reported improvement in the eosinophilic oesophagitis with an elemental diet 58. All of these diseases and disorders associated with possibly altered intestinal barrier function are pathological diseases, not what is usually associated with non-specific ‘leaky gut’.…”

Toll‐like receptor 2 stimulation augments esophageal barrier integrity

“…Epithelial barrier dysfunction plays a critical role in this process because it promotes continued exposure to allergens and microbiota in the esophageal lumen, which stimulates epithelial cells and leukocytes to release chemokines and cytokines . Decreased barrier integrity in EoE has been measured by loss of mucosal impedance in vivo and transepithelial electrical resistance in vitro …”

Evaluation of Esophageal Mucosal Integrity in Patients with Gastroesophageal Reflux Disease

“…In separate studies, Warners et al [26] used the ETIS probe in patients with eosinophilic esophagitis (EoE) and reported that eosinophilia was negatively correlated with ETIS and TEER and positively correlated with transepithelial molecule flux through biopsy specimens in Ussing chambers. Furthermore, they reported that these eosinophilia and esophageal impedance were normalized after elemental diet, and impaired expression of barrier integrity proteins (filaggrin and desmoglein-1) was also restored after diet [27]. …”