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.

Systematic review: gastric microbiota in health and disease

“…While it is generally accepted that gastro‐oesophageal reflux modifies the oesophageal microbiota, a recent study showed that this influence could be bidirectional since gastric bacteria differed between patients with normal oesophageal tissue and those with oesophagitis or BE . Gastric microbiota changes have also been associated with oesophageal cancer as higher abundance of Clostridiales and Erysipelotrichales order members were found in the gastric microbiota of early squamous dysplasia and oesophageal squamous cell cancer …”

The esophageal microbiota in health and disease

“…Concerning ESCC, a negative correlation between esophageal microbial richness and esophageal squamous dysplasia (ESD) has recently been observed using a culture‐independent approach, suggesting that individuals with a lower esophageal microbial complexity could be more prone to develop ESD. An additional study performed using an NGS approach demonstrated an enrichment in Clostridiales and Erysipelotrichales (phylum Firmicutes) in the gastric corpus microbiota of patients affected by ESD and ESCC compared with controls, pointing to a possible involvement of gastric dysbiosis in ESD–ESCC progression . Recently, a possible role for specific bacteria in the pathogenesis of ESCC has also been investigated by Gao et al ., who focused on the possible relationships between Porphyromonas gingivalis , an oral pathogen thought to be involved in oral squamous cell carcinoma tumorigenesis, and ESCC, given the histological similarity of the two cancers.…”

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications

“…They suggested that individuals with lower esophageal microbial complexity are more prone to developing esophageal squamous dysplasia 60. Another study using 16S rDNA sequencing technology demonstrated that, relative to controls, the gastric corpus microbiota of patients affected by esophageal squamous dysplasia and esophageal squamous cell carcinoma are enriched in Clostridiales and Erysipelotrichales, suggesting that gastric dysbiosis is involved in the progression from esophageal squamous dysplasia to squamous cell carcinoma 61. Gao et al 62.…”