Background: Diet is a key modifiable risk factor for esophageal squamous cell carcinoma (ESCC), while growing evidence suggests that the esophageal mucosa-associated microbiome is linked to esophageal disease progression. However, how overall plant-based diet quality relates to esophageal microbial profiles and disease severity remains unclear. 
Methods: We conducted a cross-sectional study including 236 participants undergoing upper gastrointestinal screening in a high-risk region of China. Dietary intake was assessed using food frequency questionnaire, and plant-based diet indices [overall PDI, healthful PDI (hPDI), and unhealthful PDI (uPDI)] were calculated. Esophageal mucosal swabs were collected and profiled using 16S rRNA gene sequencing. Associations between diet indices and esophageal disease severity were evaluated using regression models. Microbial diversity, differentially abundant taxa, and integrated diet microbiome risk stratification models were examined.
Results: Higher adherence to hPDI was inversely associated with esophageal disease severity, whereas higher uPDI scores were positively associated. Plant-based diet quality was linked to distinct esophageal microbial configurations, including enrichment of health-associated taxa with higher hPDI and dysbiosis-related taxa with higher uPDI. Integrating dietary indices with esophageal microbiome features modestly but consistently improved risk stratification beyond epidemiological factors alone (e.g., AUC for the combined hPDI-microbiome model was 0.93, 95%CI: 0.89-0.98).
Conclusions: Plant-based diet quality is associated with esophageal mucosa-associated microbiome profiles that align with esophageal disease severity. Integrating dietary assessment with esophageal microbial profiling may enhance population-level risk stratification and inform ESCC prevention strategies in high-risk settings.

Receiver operating characteristic (ROC) curves for discriminating AEN from non-cancer groups using dietary indices and esophageal microbiome features. The outcome was defined as pathologically confirmed AEN (HGIN + ESCC), while the reference group consist