Gastric Microbiome and Gatric Carcinogenesis: Bacterial Diversity, Co-occurrence Patterns and Predictive Models

Gastric cancer continues to be one of the most significant cancers globally. Changes in the microbiome composition and interaction have been implicated in gastric cancer development. Helicobacter pylori continue to be one most important pathogens affecting the pathogenesis of the disease; however, non Helicobacter pylori bacteria have been reported to influence the progression of the disease. Toward the understanding of how the microbiome affects the pathogenesis of the disease, many studies have provided relevant yet varying results. We present a comprehensive analysis of the gastric microbiome in gastric carcinogenesis, focusing on bacterial diversity, cooccurrence pattern, and ultimately identification of potential microbial biomarkers. We combined raw 16s rRNA data from six (6) studies across 985 samples from individuals consisting of healthy, gastritis, intestinal metaplasia and cancer. Batch effects were corrected with the Herman package in R. The gastric microbiome was dominated by Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, Acidobacteria, and Fusobacteria. However, the composition of the phyla differs with the development of gastric cancers., Differential abundance testing revealed bacteria species, mainly Sphingobium and Zoogloea, that can degrade toxic xenobiotic compounds to harmless forms were highly associated with healthy individuals. The Proteobacteria composition and diversity decrease, and the Actinobacteria increase with carcinogenesis. Transient oral pathogenic and intestinal bacteria, Prevotella, Propionibacterium acnes, Acinetobacter baumannii, lactobacillus, Gordonai polyisoprenivorans, were highly enriched with increasing carcinogenesis from gastritis to cancer. Microbial co-occurrence analysis revealed important keystone species with Pseudoxanthomonas spadix and Sphinogobium represented as hubs in healthy individuals. Filifactor alocis showed significant interaction with pathogenic bacteria Fusobacterium nucleatum in gastric cancer communities. LASSO models identified potential microbial signatures that could distinguish healthy, gastritis, intestinal metaplasia samples pairwisely with high accuracy (average ROC of 8.0). Bacteroides dorei, Hydrogenophilus hirschii, and Propionibacterium granulosum were discriminative for gastric cancer. This study provides significant insight into the gastric microbial communities and how they could serve as a potential tool for predicting gastric carcinogenesis.