Scholarlink

Background <p>Immunotherapy has transformed gastric cancer (GC) treatment, but therapeutic resistance remains a major limitation. Recent evidence suggests that the gut microbiota can modulate anti-tumor immunity and enhance immunotherapy response, offering a promising avenue to overcome resistance.</p> Methods <p>Using a prospective GC cohort, we identified <i>Eubacterium rectale</i> (<i>E. rectale</i>) as a bacterium associated with improved efficacy of tislelizumab plus chemotherapy and longer progression-free survival (PFS). We then conducted in vitro and in vivo experiments to evaluate the effects of <i>E. rectale</i> and its metabolite butyrate on tumor growth, apoptosis, PD-L1 expression, and CD8<sup>+</sup> T-cell infiltration. Targeted metabolomics was performed on gut, serum, and tumor samples to assess compartment-specific distribution of short-chain fatty acids (SCFAs).</p> Results <p><i>E. rectale</i> and butyrate significantly inhibited tumor growth, promoted apoptosis, downregulated PD-L1 expression, and increased CD8<sup>+</sup> T-cell infiltration in mouse models. Metabolomic analysis revealed that SCFAs exert antitumor effects primarily within the gut, despite cross-compartment diffusion. Furthermore, administration of <i>E. rectale</i> or butyrate led to adaptive remodeling of the gut microbiota network, characterized by a shift toward deterministic assembly processes.</p> Conclusions <p>Our study demonstrates that <i>E. rectale</i> and butyrate enhance antitumor immunity and may help overcome immunotherapy resistance in GC. These findings support a novel therapeutic strategy of combining <i>E. rectale</i> or butyrate with immunotherapy to improve treatment outcomes in GC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Butyrate-producing Eubacterium rectale inhibits gastric carcinogenesis and augments the efficacy of immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月11日

查看全文
  • Wei Gao,
  • Jiani Xiong,
  • Guangfeng Wu,
  • Yuhuang Chen,
  • Xiaoyan Lin

摘要

Background

Immunotherapy has transformed gastric cancer (GC) treatment, but therapeutic resistance remains a major limitation. Recent evidence suggests that the gut microbiota can modulate anti-tumor immunity and enhance immunotherapy response, offering a promising avenue to overcome resistance.

Methods

Using a prospective GC cohort, we identified Eubacterium rectale (E. rectale) as a bacterium associated with improved efficacy of tislelizumab plus chemotherapy and longer progression-free survival (PFS). We then conducted in vitro and in vivo experiments to evaluate the effects of E. rectale and its metabolite butyrate on tumor growth, apoptosis, PD-L1 expression, and CD8+ T-cell infiltration. Targeted metabolomics was performed on gut, serum, and tumor samples to assess compartment-specific distribution of short-chain fatty acids (SCFAs).

Results

E. rectale and butyrate significantly inhibited tumor growth, promoted apoptosis, downregulated PD-L1 expression, and increased CD8+ T-cell infiltration in mouse models. Metabolomic analysis revealed that SCFAs exert antitumor effects primarily within the gut, despite cross-compartment diffusion. Furthermore, administration of E. rectale or butyrate led to adaptive remodeling of the gut microbiota network, characterized by a shift toward deterministic assembly processes.

Conclusions

Our study demonstrates that E. rectale and butyrate enhance antitumor immunity and may help overcome immunotherapy resistance in GC. These findings support a novel therapeutic strategy of combining E. rectale or butyrate with immunotherapy to improve treatment outcomes in GC.