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-hour 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 MED, MIND, DASH, and DI-GM was associated with lower GERD risk (highest vs lowest tertile HRs 0.87-0.89), whereas a pro-inflammatory pattern (E-DII) was linked to higher risk (HR 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.