Effects of a six-food elimination diet on symptoms, quality of life, and metabolomic profile in patients with functional dyspepsia: an exploratory study.

BACKGROUND: Functional dyspepsia (FD) is a disorder of gut-brain interaction, characterized by meal-related symptoms and growing evidence of duodenal dysfunction, including compromised mucosal integrity and immune activation. While proton pump inhibitors (PPIs) are considered the first-line treatment, many patients continue to experience symptoms and are often treated with neuromodulators, which can be limited by tolerability issues. Dietary interventions targeting luminal triggers may serve as a metabolically more stable, mechanistically relevant alternative therapy. AIM: To evaluate the clinical and metabolomic effects of a six-food elimination diet combined with PPI therapy in patients with functional dyspepsia refractory to first-line treatment. METHODS: In this prospective, single-center interventional study, patients with PPI-refractory FD and healthy controls underwent a 4-week 6-food elimination diet (excluding milk, wheat, soy, eggs, nuts, and seafood). Clinical outcomes were assessed using validated questionnaires (PAGI-SYM, PAGI-QoL, PHQ-15). Plasma metabolomic profiles were analyzed using nuclear magnetic resonance spectroscopy. Pre- and post-intervention differences were evaluated using paired statistical analyses. RESULTS: Eighteen patients with FD and eighteen healthy controls completed the study. In FD patients, significant improvements were observed in upper gastrointestinal symptoms (PAGI-SYM: 1.77 to 0.77, p < 0.001), disease-specific quality of life (PAGI-QoL: 1.83 to 0.95, p < 0.01), and somatic symptom burden (PHQ-15: 9.5 to 6, p < 0.001), all with large effect sizes. A modest improvement in PHQ-15 was also observed in healthy controls. In contrast, no significant changes in plasma metabolomic profiles were detected, as supported by principal component analysis, which demonstrated substantial overlap between pre- and post-intervention samples. CONCLUSION: The results of this exploratory study suggest that a 4-week course of a six-food elimination diet, combined with PPI therapy, may be associated with symptom improvement in PPI-refractory functional dyspepsia, along with a stable metabolic environment pre- and post-intervention. However, confirmation of the positive effect of this intervention in randomized controlled trials is required before the diet can be recommended for routine clinical use, and any clinical application should be time-limited and supervised by a dietitian, with attention to the risk of restrictive eating.