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A Comparison of Tumor-Associated and Non-Tumor-Associated Gastric Microbiota in Gastric Cancer Patients

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Abstract

Background

How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC.

Methods

Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses.

Results

GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community.

Conclusions

GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of Helicobacter spp. may be the primary driver of gastric dysbiosis in GC patients.

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Acknowledgments

This work was supported by the Natural Science Foundation of Jiangsu Commission of Health (K2019029); Youth Projects of Jiangsu traditional Chinese Medicine Hospital (Y2018CX83); Jiangsu Province Graduate Student Practice Innovation Plan (SJCX19_0402).

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Authors and Affiliations

  1. Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China

    Zhen-Feng Wu, Kun Zou, Guan-Nan Wu, Zhao-Jia Jin, Xiao-Yu Wu, Che Chen, Zhe Xu, Wei-Su Li, Xue-Quan Yao & Fu-Kun Liu

  2. School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing, 210023, People’s Republic of China

    Chun-Jie Xiang, Shuo Xu & Jun-Feng Zhang

  3. Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China

    Yao-Hui Wang

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  1. Zhen-Feng Wu
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  2. Kun Zou
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Correspondence to Xue-Quan Yao.

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10620_2020_6415_MOESM1_ESM.pdf

Supplementary Figure S1: Beta diversity analysis of the gastric microbiota. PCoA plots of the unweighted (A) and weighted (B) UniFrac distances in the full sample set in which samples were coloured by increasing age. Mantel correlations controlled with 104 permutations were used to compare distances. PCoA plots of the unweighted (C) and weighted UniFrac (D) distances in the full sample set. Samples were coloured by gender (PDF 372 kb)

10620_2020_6415_MOESM2_ESM.pdf

Supplementary Figure S2: PCoA plots of the unweighted (A) and weighted (B) UniFrac distances in gastric carcinoma. Samples were coloured by histological type. PCoA plots of the unweighted (C) and weighted (D) UniFrac distances in gastric carcinoma. Samples were coloured by tumour location. PCoA plots of the unweighted (E) and weighted (F) UniFrac distances of non-tumor tissue in gastric carcinoma. Samples were coloured by stomach anatomic sites. PCoA plots of the unweighted (G) and weighted (H) UniFrac distances in superficial gastritis. Samples were coloured by stomach anatomic sites (PDF 471 kb)

10620_2020_6415_MOESM3_ESM.pdf

Supplementary Figure S3: Different bacterial taxa in tumor and non-tumor tissues of gastric cancer patients. (A) Differential bacteria between the tumor and non-tumor tissues of gastric cancer patients by LEfSe analysis (LDA scores >3.0). Green indicates taxa enriched in tumor tissues and red indicates taxa enriched in non-tumor tissues. (B) Cladogram representation of the gastric microbiota taxa associated with tumor and non-tumor tissues of gastric cancer patients (PDF 1892 kb)

Supplementary material 4 (XLSX 14 kb)

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Wu, ZF., Zou, K., Wu, GN. et al. A Comparison of Tumor-Associated and Non-Tumor-Associated Gastric Microbiota in Gastric Cancer Patients. Dig Dis Sci 66, 1673–1682 (2021). https://doi.org/10.1007/s10620-020-06415-y

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  • DOI: https://doi.org/10.1007/s10620-020-06415-y

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