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Objective <p>Increasing evidence indicated substantial involvement of non-<i>Helicobacter pylori</i> microbiota in gastric tumorigenesis. We aimed to elucidate detailed relationship of microbiome dynamics between two different steps in gastric cancer (GC) such as cancer initiation and progression, and assessed their associations with clinicopathological and molecular changes.</p> Methods <p>We systemically characterized gastric microbiome during GC initiation and progression using 944 biopsies from primary GC, non-cancerous gastric mucosa from both GC and non-cancer subjects. The association between specific microbial characteristics and GC risk, prognosis and molecular changes such as <i>TP53</i> mutation, DNA methylation and telomere shortening were also evaluated.</p> Results <p>Microbial α-diversity in the gastric mucosa was decreased in relation to the GC occurrence, while it increased in primary GC tissue. Such paradoxical change was also observed in specific groups of bacteria during GC occurrence and its progression. GC risk-related microbiome was associated with differentiated GC, severe intestinal metaplasia, associated DNA methylation and telomere shortening, while GC tissue-specific microbiome was associated with more aggressive features of GC and <i>TP53</i> mutation status.</p> Conclusions <p>Our findings suggested the different role of non-<i>Helicobacter pylori</i> microbiota in GC initiation and progression steps.</p>

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Gastric microbiome in gastric cancer sequence depicts diverse microbial structures associated with cancer risk and prognosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月1日

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  • Tsubasa Shimogama,
  • Tomomitsu Tahara,
  • Takuya Shijimaya,
  • Jumpei Yamazaki,
  • Sanshiro Kobayashi,
  • Naohiro Nakamura,
  • Yu Takahashi,
  • Takashi Tomiyama,
  • Yusuke Honzawa,
  • Toshiro Fukui,
  • Makoto Naganuma

摘要

Objective

Increasing evidence indicated substantial involvement of non-Helicobacter pylori microbiota in gastric tumorigenesis. We aimed to elucidate detailed relationship of microbiome dynamics between two different steps in gastric cancer (GC) such as cancer initiation and progression, and assessed their associations with clinicopathological and molecular changes.

Methods

We systemically characterized gastric microbiome during GC initiation and progression using 944 biopsies from primary GC, non-cancerous gastric mucosa from both GC and non-cancer subjects. The association between specific microbial characteristics and GC risk, prognosis and molecular changes such as TP53 mutation, DNA methylation and telomere shortening were also evaluated.

Results

Microbial α-diversity in the gastric mucosa was decreased in relation to the GC occurrence, while it increased in primary GC tissue. Such paradoxical change was also observed in specific groups of bacteria during GC occurrence and its progression. GC risk-related microbiome was associated with differentiated GC, severe intestinal metaplasia, associated DNA methylation and telomere shortening, while GC tissue-specific microbiome was associated with more aggressive features of GC and TP53 mutation status.

Conclusions

Our findings suggested the different role of non-Helicobacter pylori microbiota in GC initiation and progression steps.