Bacterial overgrowth and diversification of microbiota in gastric cancer

Lili Wang, Jianhua Zhou, Yongning Xin, Changxin Geng, Zibin Tian, Xinjuan Yu, Quanjiang Dong, Lili Wang, Jianhua Zhou, Yongning Xin, Changxin Geng, Zibin Tian, Xinjuan Yu, Quanjiang Dong

Abstract

Objective: Microbiota is potentially linked to the development of cancer. However, the features of microbiota in gastric cancer remain unclear. The aim of this study was to characterize the gastric microbiota in cancer.

Methods: A total of 315 patients, including 212 patients with chronic gastritis and 103 patients with gastric cancer, were enrolled in the study. The bacterial load of gastric mucosa was determined using quantitative PCR. To analyze the biodiversity, structure, and composition of microbiota, amplicons of the 16S rRNA gene from 12 patients were pyrosequenced. The sequences were processed and subsequently analyzed.

Results: The amount of bacteria in gastric mucosa was estimated to be 6.9×10 per gram tissue on average. It was higher in Helicobacter pylori-infected patients (7.80±0.71) compared with those uninfected (7.59±0.57, P=0.005). An increased bacterial load up to 7.85±0.70 was detected in gastric cancer compared with chronic gastritis (P=0.001). The unweighted principal coordinate analysis showed that the structure of microbiota in gastric cancer was more diversified. Five genera of bacteria with potential cancer-promoting activities were enriched in gastric cancer. The weighted principal coordinate analysis showed that the presence of Helicobacter pylori markedly altered the structure of microbiota, but had little influence on the relative proportions of the other members in the microbiota.

Conclusion: Findings from this study indicated an altered microbiota in gastric cancer with increased quantity of bacteria, diversified microbial communities, and enrichment of bacteria with potential cancer-promoting activities. These alterations could contribute toward the gastric carcinogenesis.

Figures

Fig. 1
Fig. 1
Correlation of the bacterial load in gastric mucosa with H. pylori. Bacterial load and quantity of H. pylori were determined using quantitative PCR. The amount was calculated as copy numbers of the 16S rRNA gene (or ureB for H. pylori) per microgram DNA. Linear regression analysis found that the bacterial load was positively, although weakly, correlated with the quantity of H. pylori in gastric mucosa (R=0.38, P<0.001). H. pylori, Helicobacter pylori.
Fig. 2
Fig. 2
The bacterial load in gastric cancer. The bacterial load of eubacteria in gastric cancer and chronic gastritis was determined using quantitative PCR. The amount was calculated as copy numbers of 16S rRNA gene per microgram of DNA.
Fig. 3
Fig. 3
The unweighted (a) and weighted (b) principal coordinate (PC) analysis of microbiota from gastric cancer and chronic gastritis using Fast UniFrac analysis. H. pylori-positive individuals are indicated by filled circles or triangles. H. pylori, Helicobacter pylori.
Fig. 4
Fig. 4
Compositions of gastric microbiota at the phylum level. High-throughput sequencing of amplicons of the 16S rRNA gene was performed on 12 samples from patients with chronic gastritis (201–206) and gastric cancer (207–212).

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