Esophageal microecology: unraveling the mechanisms underlying esophageal cancer and precancerous lesions

Esophageal cancer is a common and lethal digestive malignancy worldwide. Despite advances in imaging and endoscopy, most patients are diagnosed at intermediate or advanced stages and have poor long-term outcomes. Perturbations of the oral, esophageal, and intestinal microbiota have emerged as potential risk factors for esophageal cancer and its precursors, although studies remain highly heterogeneous in populations, sampling methods, and analytical strategies. This review synthesises current evidence on the microecological features of the normal esophagus, with a primary focus on esophageal squamous intraepithelial neoplasia (ESIN)—synonymous with dysplasia—and esophageal squamous cell carcinoma (ESCC). Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) are also examined selectively for comparative purposes to highlight distinct microenvironmental trajectories. We examine potential microbiota-mediated mechanisms, including chronic inflammation, immune modulation, metabolic alterations, genotoxicity, bacteria–fungus interactions, and bacteriophage-driven remodelling of host–microbe networks, and discuss translational opportunities to improve clinical outcomes.