Abstract

Objective: Dysbiosis of gastric microbiota such as Helicobacter pylori plays a significant role in pathogenesis and progression of gastric cancer. Our aim was to evaluate the composition and functional effects of gastric microbiota in superficial gastritis (SG) and advanced gastric adenocarcinoma (GC).Methods: We carried out shotgun metagenomic sequencing on gastric wash samples from 6 patients with GC and 5 patients with SG. The taxonomic composition was profiled using MetaPhlAn2 and functional gene pathway was profiled using HUMAnN2. Differences in microbial composition and pathways between the two patient groups were assessed via LEfSe.Results: The gastric microbiota in GC patients was characterized by reduced species richness, enrichment of 13 bacterial taxa and depletion of 31 taxa (q < 0.05). The most representative taxa which were abundant in GC corresponded to the commensals or opportunistic pathogens that usually colonize the oral cavity, including genera Neisseria, Alloprevotella, and Aggregatibacter, species Streptococcus_mitis_oralis_pneumoniae and strain Porphyromonas_endodontalis.t_GCF_000174815. Each of the three GC-associated genera could separate GC from SG completely. In particular, Sphingobium yanoikuyae, a bacterium capable of degrading carcinogenic compounds, was depleted in GC. Functionally, pathways associated with the biosynthesis of lipopolysaccharide (LPS) and L-arginine were enriched in GC, whereas pathways involved in the fermentation of short chain fatty acids (SCFAs) and branched amino acid metabolism were more abundant in SG.Conclusions: Our results present new alterations in the gastric microbiome in patients with GC from a whole-genome perspective, suggesting that microbiome composition and function can be used for prognosis and diagnosis of GC.

Highlights

  • Gastric cancer is the third leading cause of cancer-related deaths worldwide, with an estimated 1 million new cases recorded yearly, and half of these cases occurring in Eastern Asia (Torre et al, 2015)

  • We compared the gastric microbiome of patients with Advanced gastric adenocarcinoma (GC) and Superficial gastritis (SG) by shotgun metagenomics analysis

  • A total of 11 subjects were included with matched age, sex and body mass index (BMI) between GC(n = 6) and SG(n = 5) groups (Table 1, Supplementary Table 1)

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Summary

Introduction

Gastric cancer is the third leading cause of cancer-related deaths worldwide, with an estimated 1 million new cases recorded yearly, and half of these cases occurring in Eastern Asia (Torre et al, 2015). H. pylori-induced inflammation and injury can progressively destroy the architecture and function of the gastric epithelium (Amieva and Peek, 2016). Successful eradication of H. pylori does not completely prevent the development of gastric carcinoma, and only ∼1% of those infected develop gastric cancer (Ma et al, 2012; Lee et al, 2016; Shah, 2017). These statistics suggest that other factors might be involved in the carcinogenesis of gastric cancer and further investigation is required

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