Prospective study of an amino acid-based elemental diet in an eosinophilic gastritis and gastroenteritis nutrition trial

Abstract

Background: Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically.

Objective: We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE.

Methods: Adults aged 18 to 65 years with histologically active EoG/EoGE (≥30 eosinophils per high-power field) in the stomach and/or duodenum and gastrointestinal symptoms within the month preceding enrollment were prospectively enrolled onto a single-arm clinical trial to receive elemental formula for 6 consecutive weeks. The primary end point was percentage of participants with complete histologic remission (<30 eosinophils per high-power field in both stomach and duodenum). Exploratory outcomes were improvement in symptoms, endoscopy results, blood eosinophilia, quality of life, Physician Global Assessment score, and EoG-relevant gastric transcriptome and microbiome.

Results: Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. Multi-gastrointestinal segment involvement affected 87%. All subjects had complete histologic remission in the stomach (P = .002) and duodenum (P = .001). Scores improved in overall PhGA (P = .002); EGREFS (P = .003); EGDP (P = .002); SODA pain intensity (P = .044), non-pain (P = .039), and satisfaction (P = .0024); and PROMIS depression (P = .0078) and fatigue (P = .04). Food reintroduction reversed these improvements. The intervention was well tolerated in 14 subjects, with 1 serious adverse event reported in 1 subject.

Conclusion: An amino acid-based elemental diet improves histologic, endoscopic, symptomatic, quality-of-life, and molecular parameters of EoG/EoGE; these findings and disease recurrence with food trigger reintroduction support a dominant role for food allergens in disease pathogenesis.

Clinicaltrials: gov Identifier: NCT03320369.

Keywords: Eosinophilic gastritis; elemental diet; eosinophilia; eosinophilic gastroenteritis; food allergy.

Figure 1.. Eosinophilic inflammation pre and post 6-week elemental diet.

Individual data are shown as dots; data pairs from the same subjects are connected. Red bars show the means pre and post treatment. Mean paired change (95% confidence level [CL]) is shown and tested against 0 using the paired t test. Each line represents a different participant. The horizontal red line depicts the mean eosinophil levels pre and post therapy. Eos/hpf, eosinophils per high-power microscopic field of gastric or duodenal biopsy. Eosinophil levels at baseline in some patients may have been under 30 in one location as entry criteria included threshold levels in either location, not both. One patient had an increase in eosinophil levels in the stomach but both levels were subthreshold for meeting criteria for EoG. This patient had duodenal eosinophilia which met entry criteria.

Figure 2.. Endoscopic features by EGREFS pre and post 6-week elemental diet.

Individual data are shown as dots; data pairs from the same subjects are connected. Red bars show the medians pre and post treatment. Median and interquartile range (IQR) of the paired change are shown as the red triangle and vertical bars, respectively. Paired change was tested against 0 using the Wilcoxon signed rank test.

Figure 3.. Representative endoscopies and peripheral eosinophilia.

A, Representative endoscopies. In Subject 1, gastric improvement in Friability and Erythema is noted post treatment. In Subject 2, gastric improvement in Granularity, Friability, Thickened Folds, and Raised Lesions are noted post treatment. In Subject 3, duodenal improvement in denuded patches are noted post treatment. B, Peripheral eosinophilia. Individual data are shown as dots; data pairs from the same subjects are connected. Red bars show the medians pre and post treatment. Individual and median paired change (interquartile range [IQR]) are shown as the red triangle and vertical bars, respectively. Paired change of peripheral eosinophilia was tested against 0 using the Wilcoxon signed rank test. Eos, eosinophils.

Figure 4.. Molecular efficacy of 6-week elemental diet in EoG.

A, Paired comparison of EGDP18 score are plotted by groups for pre and post treatment. Markers represent individual subjects. EGDP18 score is inversely correlated with disease severity, with an increase representing an improvement. **P < 0.01 using the Wilcoxon matched-pairs signed rank test. B–C, Heat diagram of a diagnostic subset of genes from the EoG transcriptome (EGDP). B, Each column indicates collective gastric biopsy specimens taken from subjects pre (left) and post treatment (right) in this prospective trial (ELEMENT study). C, Consecutive columns indicate gastric biopsy specimens taken from subjects of historic cohort (left, positive control) and pre and post treatment in this prospective trial (ELEMENT study) (right). D, Differences in gene expression between pre and post treatment. The y axis represents the negative log10 P value determined by differential expression; red indicates genes significantly improved post versus pre treatment. The x axis is organized by genes within functional groupings. NL, healthy control

Figure 5.. Improvement of EGHSS and tissue eosinophilia after 6-week elemental diet and tissue eosinophilia recurrence with reintroduction of the triggering food.

(A) Individual data are shown as dots; data pairs from the same subjects are connected. Red bars separately show the means of EGHSS pre and post treatment. Individual and mean paired change (95% confidence level [CL]) was shown and tested against 0 using the paired t test. (B) Shown is tissue eosinophilia in the stomach (left) and duodenum (middle) and peripheral eosinophilia (right); note resolution of tissue and peripheral eosinophilia after elemental diet and recurrence with food trigger reintroduction (reintro). Eos/hpf, eosinophils per high-power microscopic field of gastric or duodenal biopsy.