Dietary patterns, metabolomics and incident gastroesophageal reflux disease: a prospective cohort study.

Prospective evidence linking overall diet quality to gastroesophageal reflux disease (GERD) is limited, and metabolic pathways remain unclear. In a cohort of 183 878 adults free of GERD at baseline, we examined nine dietary pattern scores derived from repeated 24-h dietary recalls and assessed associations with incident GERD over a median follow-up of 13·2 years, during which 15 401 cases occurred. Higher adherence to healthy patterns including Mediterranean diet, Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay, Dietary Approaches to Stop Hypertension and dietary index for gut microbiota was associated with lower GERD risk (highest v. lowest tertile hazard ratios 0·87-0·89), whereas a pro-inflammatory pattern (Energy-adjusted Diet Inflammatory Index) was linked to higher risk (hazard ratio 1·11). In a metabolomics sub-cohort (N 98 669), diet-related NMR metabolomic signatures, derived from 168 biomarkers using Elastic Net regression, reflected similar associations and mediated 11·1-32·2 % of the diet-GERD relationship. Associations were largely consistent across subgroups and robust in sensitivity analyses, supporting a potential role of systemic metabolic profiles in mediating the effects of diet on GERD and highlighting metabolic mechanisms underlying diet-related disease risk.