Abstract

The link between microbiota and gastric cancer (GC) has attracted widespread attention. However, the phylogenetic profiles of niche-specific microbiota in the tumor microenvironment is still unclear. Here, mucosa-associated microorganisms from 62 pairs of matched GC tissues and adjacent non-cancerous tissues were characterized by 16S rRNA gene sequencing. Functional profiles of the microbiota were predicted using PICRUSt, and a co-occurrence network was constructed to analyze interactions among gastric microbiota. Results demonstrated that mucosa-associated microbiota from cancerous and non-cancerous tissues established micro-ecological systems that differed in composition, structure, interaction networks, and functions. Microbial richness and diversity were increased in cancerous tissues, with the co-occurrence network exhibiting greater complexity compared with that in non-cancerous tissue. The bacterial taxa enriched in the cancer samples were predominantly represented by oral bacteria (such as Peptostreptococcus, Streptococcus, and Fusobacterium), while lactic acid-producing bacteria (such as Lactococcus lactis and Lactobacillus brevis) were more abundant in adjacent non-tumor tissues. Colonization by Helicobacter pylori, which is a GC risk factor, also impacted the structure of the microbiota. Enhanced bacterial purine metabolism, carbohydrate metabolism and denitrification functions were predicted in the cancer associated microbial communities, which was consistent with the increased energy metabolism and concentration of nitrogen-containing compounds in the tumor microenvironment. Furthermore, the microbial co-occurrence networks in cancerous and non-cancerous tissues of GC patients were described for the first time. And differential taxa and functions between the two groups were identified. Changes in the abundance of certain bacterial taxa, especially oral microbiota, may play a role in the maintenance of the local microenvironment, which is associated with the development or progression of GC.

Highlights

  • MATERIALS AND METHODSGastric cancer (GC) is one of the most common malignant cancers and the third leading cause of cancer-associated death worldwide (Ferlay et al, 2015; Torre et al, 2015)

  • After sequencing and quality control, libraries of 16S rRNA gene V4–V5 region amplicon sequences from cancerous and adjacent non-cancerous tissue samples were used for further analysis, with an average of 67,958 effective tags per sample

  • Given that the accumulation of nitrogen-containing compounds such as nitrate and nitrite in the stomach can increase the risk of gastric cancer (GC) and promote the malignant transformation of cells in the stomach (Correa, 1992; Alarcon et al, 2017), we focused on the microbial functions relevant to the metabolism of nitrogen-containing compounds in the cancerous and non-cancerous tissues

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Summary

Introduction

Gastric cancer (GC) is one of the most common malignant cancers and the third leading cause of cancer-associated death worldwide (Ferlay et al, 2015; Torre et al, 2015). The incidence of GC varies by region and race, with a high rate in East Asia. Both host factors (such as genetic susceptibility) and environmental factors (such as microbial infections) play crucial roles in gastric tumorigenesis (Compare et al, 2010). It is widely accepted that chronic Helicobacter pylori infection, which leads to enhanced inflammation and disorders of epithelial structure and function, is closely related to precancerous lesions such as atrophic gastritis. Biological factors other than H. pylori colonization may play an important role in the development of cancer and the maintenance of the local lesion microenvironment

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