Plant-based diet quality is associated with esophageal mucosa-associated microbiome profiles and disease severity in a high-risk Chinese population.

Background: Esophageal squamous cell carcinoma (ESCC) remains a major public health challenge in China. Diet is a modifiable risk factor, and the esophageal mucosa-associated microbiome may contribute to esophageal disease progression. However, population-based evidence integrating plant-based diet quality, esophageal microbiome profiles anddisease severity remains limited. Methods: We conducted a cross-sectional study including 236 participants undergoing upper gastrointestinal screening in Linzhou, a high-risk region for ESCC. Dietary intake was assessed using a food frequency questionnaire, and plant-based diet indices, including the overall plant-based diet index (PDI), healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI), were calculated. Esophageal mucosal swabs were profiled by 16S rRNA gene sequencing. Associations among diet indices, microbiome features, and esophageal disease severity were evaluated using regression and risk stratification models. Results: Higher hPDI was inversely associated with esophageal disease severity, whereas higher uPDI were positively associated. Higher hPDI was associated with greater relative abundance of Rothia and Prevotellaceae-related taxa, whereas higher uPDI was associated with enrichment of Streptobacillus and Fretibacterium. Integrating dietary indices with 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: Healthful and unhealthful plant-based diet patterns showed opposite associations with esophageal disease severity and distinct mucosa-associated microbiome profiles, supporting an exploratory diet-microbiome framework for ESCC risk stratification.