The Potential Role of Compounds Derived From Ultra-processed Foods in Pathogenesis of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic antigen-mediated inflammatory disease of the esophagus that affects both children and adults. The incidence and prevalence of EoE is rapidly increasing in Western countries with an estimated incidence of 6.6 per 100,000 person-years (95% CI, 3-11.7) in children and 7.7 per 100,000 person-years (95% CI, 1.8-17.8) in adults. Clinically, it is characterized by various symptoms related to esophageal dysfunction, including vomiting, regurgitation, feeding difficulties, epigastric heartburn, dysphagia, or food bolus impaction, and may cause growth retardation. Diagnosis is made on the basis of clinical symptoms and histological evidence of eosinophilic infiltration of the esophagus (at least 15 eosinophils/high power microscope field (eos /hpf), excluding other etiologies of esophageal eosinophilia (gastroesophageal reflux disease, infectious esophagitis, achalasia, celiac disease and Crohn's disease, connective tissue disorders, gra ft versus host disease, drug hypersensitivity and hypereosinophilic syndromes). EoE is primarily characterized by a T helper 2 type inflammation, but the pathogenesis and the immunopathological mechanisms underlying the pathology are not yet fully understood. Recent evidence suggests that in genetically predisposed individuals, interaction with environmental factors (e.g., dietary lifestyle) may play a role in activating several inflammatory pathways and cause EoE.

Ultra-processed foods (UPFs) are food and beverage products resulting from industrial formulations, ready for consumption, typically obtained with five or more ingredients from different manufacturing processes (cooking methods, addition of additives such as stabilizers or preservatives). During the last decade, the consumption of the latter has increased significantly among the pediatric population to represent 30% of the daily caloric intake of an average child in Europe and America. Recent evidences show that UPFs favor the onset of chronic non-communicable diseases through the activation of different inflammatory pathways.

The components mostly represented in UPFs are the advanced glycation end products (AGEs), a heterogeneous group of highly oxidizing compounds that are formed through non-enzymatic reactions (Maillard reaction) between reduced sugars and free amino groups of proteins, lipids, or nucleic acids.

Evidence demonstrates that dietary AGEs are absorbed and contribute significantly to the total concentration of AGEs in the body. AGEs induce oxidative stress and inflammation, leading to structural and functional protein alterations, cellular apoptosis and multi-tissue/organ damage. These mechanisms are mediated at least in part by interactions with their cell-surface receptor for advanced glycation end-products (RAGE).

The AGEs-RAGE interaction modulates the immune response. AGEs are able to activate le mast cells, to stimulate the release of histamine and to induce a chronic inflammatory state that promotes a T helper 2 type response.

Study Overview

• Status: Recruiting
• Conditions: Esophagitis, Eosinophilic
• Intervention / Treatment: Other: Dietary evaluation

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • Recruiting
    • Department of Traslational Medical Science - University of Naples Federico II
    • Contact: Roberto Berni Canani; Phone Number: 0817462680; Email: berni@unina.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients both sexes, aged between 3-65 years with diagnosis of eosinophilic esophagitis and age- and sex-matched healthy controls

Description

Inclusion Criteria:

• both sexes
• age between 3-65 years
• sure diagnosis of eosinophilic esophagitis
• age- and sex-matched healthy controls
• parents/tutor written informed consent.

Exclusion Criteria:

• lack of written informed consent;
• non-Caucasian ethnicity
• age at enrollment < 3 or >65 years
• simultaneous presence of other chronic diseases: eosinophilic gastroenteritis, eosinophilic colitis, achalasia, GERD, hypereosinophilia syndrome, IBD, fungal or viral infections, connective tissue disorders, autoimmune diseases, vasculitis, bullous dermatosis with oesophageal involvement (pemphigus), drug hypersensitivity reactions, drug-induced oesophagitis, graft vs host disease, monogenic disorders (Marfan syndrome type 2, HIES, PTEN).
• presence of tattoos, scars, moles or particular lesions on both forearms

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sex and age matched healthy controls; Matched healthy controls for age and gender, without eosinophilic esophagitis	Other: Dietary evaluation; Comparative evaluation of the dietary consumption of ultraprocessed foods and ultraprocessed foods-derived compounds
Patients with eosinophilic esophagitis; Patients with a sure diagnosis of eosinophilic esophagitis	Other: Dietary evaluation; Comparative evaluation of the dietary consumption of ultraprocessed foods and ultraprocessed foods-derived compounds

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparative evaluation of the dietary consumption of Ultraprocessed Foods	A 7-day food diary to evaluate the dietary intake of ultraprocessed foods.	At enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intake of dietary Advanced Glycation End-products	A 7-day food diary to evaluate the dietary intake of the detrimental compounds of ultraprocessed foods, the advanced glycation end-products.	At enrollment
Skin Advanced Gycation End-products accumulation level	AGEs reader to evaluate the skin Advanced Gycation End-products accumulation level. Skin AGEs levels will be calculated as the ratio between the emission light and reflected excitation light, multiplied by 100 and expressed in arbitrary units (AU).	At enrollment
Advanced Glycation End-Products receptor (RAGE) expression in peripheral blood mononuclear cells (PBMCs)	ELISA test.	At enrollment
Advanced Glycation End-Products receptor (RAGE) expression in plasma	ELISA test	At enrollment
Advanced Glycation End-Products receptor (RAGE) expression in peripheral blood mononuclear cells (PBMCs)	flow cytometry	At enrollment
Disease severity	Pediatric Eosinophilic Esophagitis Symptom Scores (PEES Score)	At 3 months, at 6 months
Disease severity	Eosinophilic Esophagitis Endoscopic Reference Score (EREFS Score)	At 3 months, at 6 months
Treatment response	Drug used for inducing eosinophilic esophagitis remission defined as <15 eosinophils per high-power field (eos/hpf)	At 3 months, at 6 months

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Actual): June 12, 2025
• Study Completion (Estimated): June 12, 2026

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Hypersensitivity, Immediate; Hypersensitivity; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Esophageal Diseases; Gastroenteritis; Esophagitis; Eosinophilic Esophagitis
• Other Study ID Numbers: 00014834

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No