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Background <p>Gut microbiota plays a pivotal role in modulating therapeutic responses in malignancies. Elucidating microbial dynamics during cancer treatment provides critical insights for optimizing therapeutic strategies and prognostic prediction.</p> Purpose <p>To investigate longitudinal alterations in oral and gut microbiota during chemotherapy in advanced gastric cancer (GC) patients and their prognostic implications.</p> Methods <p>This study enrolled 29 advanced GC patients, with tongue coating and fecal samples collected before the 1st (GC0), 2nd (GC1), and 3rd (GC2) chemotherapy cycles, alongside 35 healthy controls. Bacterial communities were profiled via 16&#xa0;S rRNA V3-V4 sequencing, and fungal communities via 18&#xa0;S rRNA ITS1-ITS2 sequencing. LEfSe, ROC analysis, Zero-Inflated Beta Regression (ZIBR) modeling, and co-occurrence network analysis were employed to evaluate microbial dynamics and prognostic utility.</p> Results <p>During chemotherapy, oral fungal and gut bacterial richness (ACE and Chao indices) significantly decreased, while gut fungal richness increased. β-diversity analysis revealed minimal structural alterations in oral-gut microbiota. The abundance of intestinal bacterial <i>Subdoligranulum</i> genus and the fungal <i>Candida</i> (in both intestine and oral cavity) exhibited a decreasing trend, whereas the abundance of intestinal bacterial genera including <i>Escherichia-Shigella</i> and <i>Streptococcus</i> significantly increased (<i>P</i> &lt; 0.05) during chemotherapy in patients with advanced GC. In the GC0 group, 23 genera (e.g., oral/gut <i>Bacillus</i>, oral <i>Veillonella</i>) predicted 12-month progression-free survival (PFS) (AUC &gt; 0.7). Longitudinal analysis identified 25 genera (e.g., oral <i>Clostridium_sensu_stricto_1</i>, gut <i>Bacillus</i> and <i>Howardella</i>) significantly associated with PFS across GC0-GC2 (Joint <i>P</i> &lt; 0.05). Co-occurrence networks demonstrated oral bacterial dominance in GC patients, with chemotherapy reducing network complexity.</p> Conclusion <p>Continuous chemotherapy exerted significant effects on the oral-gut microbiota co-occurrence networks in advanced GC patients, with pre-chemotherapy microbiota demonstrating prognostic diagnostic value. This study provided microbiological evidence to inform future GC monitoring and personalized therapeutic strategies.</p>

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Longitudinal analysis of postoperative chemotherapy on oral-gut microbiota in patients with advanced gastric cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月16日

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  • Shuo Xu,
  • Bingbing Li,
  • Yingxin Yang,
  • Zhijuan Tan,
  • Zhaoling Wang,
  • Bin Lu,
  • Jianping Wu,
  • Chun Cheng,
  • Zhenfeng Wu,
  • Junfeng Zhang

摘要

Background

Gut microbiota plays a pivotal role in modulating therapeutic responses in malignancies. Elucidating microbial dynamics during cancer treatment provides critical insights for optimizing therapeutic strategies and prognostic prediction.

Purpose

To investigate longitudinal alterations in oral and gut microbiota during chemotherapy in advanced gastric cancer (GC) patients and their prognostic implications.

Methods

This study enrolled 29 advanced GC patients, with tongue coating and fecal samples collected before the 1st (GC0), 2nd (GC1), and 3rd (GC2) chemotherapy cycles, alongside 35 healthy controls. Bacterial communities were profiled via 16 S rRNA V3-V4 sequencing, and fungal communities via 18 S rRNA ITS1-ITS2 sequencing. LEfSe, ROC analysis, Zero-Inflated Beta Regression (ZIBR) modeling, and co-occurrence network analysis were employed to evaluate microbial dynamics and prognostic utility.

Results

During chemotherapy, oral fungal and gut bacterial richness (ACE and Chao indices) significantly decreased, while gut fungal richness increased. β-diversity analysis revealed minimal structural alterations in oral-gut microbiota. The abundance of intestinal bacterial Subdoligranulum genus and the fungal Candida (in both intestine and oral cavity) exhibited a decreasing trend, whereas the abundance of intestinal bacterial genera including Escherichia-Shigella and Streptococcus significantly increased (P < 0.05) during chemotherapy in patients with advanced GC. In the GC0 group, 23 genera (e.g., oral/gut Bacillus, oral Veillonella) predicted 12-month progression-free survival (PFS) (AUC > 0.7). Longitudinal analysis identified 25 genera (e.g., oral Clostridium_sensu_stricto_1, gut Bacillus and Howardella) significantly associated with PFS across GC0-GC2 (Joint P < 0.05). Co-occurrence networks demonstrated oral bacterial dominance in GC patients, with chemotherapy reducing network complexity.

Conclusion

Continuous chemotherapy exerted significant effects on the oral-gut microbiota co-occurrence networks in advanced GC patients, with pre-chemotherapy microbiota demonstrating prognostic diagnostic value. This study provided microbiological evidence to inform future GC monitoring and personalized therapeutic strategies.