Variations of gastric corpus microbiota are associated with early esophageal squamous cell carcinoma and squamous dysplasia

Abstract

Observational studies revealed a relationship between changes in gastric mucosa and risk of esophageal squamous cell carcinoma (ESCC) which suggested a possible role for gastric microbiota in ESCC carcinogenesis. In this study we aimed to compare pattern of gastric corpus microbiota in ESCC with normal esophagus. Cases were included subjects with early ESCC (stage I-II) and esophageal squamous dysplasia (ESD) as the cancer precursor. Control groups included age and sex-matched subjects with mid-esophagus esophagitis (diseased-control), and histologically normal esophagus (healthy-control). DNA was extracted from snap-frozen gastric corpus tissues and 16S rRNA was sequenced on GS-FLX Titanium. After noise removal, an average of 3004 reads per sample was obtained from 93 subjects. We applied principal coordinate analysis to ordinate distances from beta diversity data. Pattern of gastric microbiota using Unifrac (p = 0.004) and weighted Unifrac distances (p = 0.018) statistically varied between cases and healthy controls. Sequences were aligned to SILVA database and Clostridiales and Erysipelotrichales orders were more abundant among cases after controling for multiple testing (p = 0.011). No such difference was observed between mid-esophagitis and healthy controls. This study is the first to show that composition of gastric corpus mucosal microbiota differs in early ESCC and ESD from healthy esophagus.