Evaluation of the Oesophagogastric Cancer-Associated Microbiome: A Systematic Review and Quality Assessment

SIMPLE SUMMARY: Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. Emerging data suggest that bacteria specific to cancer may play a role in earlier disease detection and treatment strategies. This study aimed to evaluate all microbiome studies identifying bacteria enriched in oesophagogastric cancer and appraisal of the methods. Eighty-nine studies demonstrated an enrichment of five bacteria in gastric cancer (Lactobacillus, Streptococcus, Prevotella, Fusobacterium, Veillonella) and three bacteria in oesophageal squamous cell carcinoma (Streptococcus, Prevotella, Fusobacterium). No differences were observed in oesophageal adenocarcinoma. Functional analysis supports the role of immune cells, localised inflammation and cancer-specific pathways in cancer progression. There is evidence that batch effects and contamination in sample analysis are poorly reported. The STORMS checklist provides a framework for high-quality microbiome studies. Whole-genome sequencing is recommended to provide key metabolic and functional pathway analysis of potentially important bacteria influencing cancer progression. ABSTRACT: Objective. Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. The role of bacteria in the pathogenesis of oesophagogastric cancer remains poorly understood. Design. A systematic search identified studies assessing the oesophagogastric cancer microbiome. The primary outcome was to identify bacterial enrichment specific to oesophagogastric cancer. Secondary outcomes included appraisal of the methodology, diagnostic performance of cancer bacteria and the relationship between oral and tissue microbiome. Results. A total of 9295 articles were identified, and 87 studies were selected for analysis. Five genera were enriched in gastric cancer: Lactobacillus, Streptococcus, Prevotella, Fusobacterium and Veillonella. No clear trends were observed in oesophageal adenocarcinoma. Streptococcus, Prevotella and Fusobacterium were abundant in oesophageal squamous cell carcinoma. Functional analysis supports the role of immune cells, localised inflammation and cancer-specific pathways mediating carcinogenesis. STORMS reporting assessment identified experimental deficiencies, considering batch effects and sources of contamination prevalent in low-biomass samples. Conclusions. Functional analysis of cancer pathways can infer tumorigenesis within the cancer–microbe–immune axis. There is evidence that study design, experimental protocols and analytical techniques could be improved to achieve more accurate and representative results. Whole-genome sequencing is recommended to identify key metabolic and functional capabilities of candidate bacteria biomarkers.