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<p>Recent studies indicate the gut microbiome as a crucial regulator of cancer therapy, yet its role in urological malignancies remains incompletely understood. High rates of resistance to cornerstone treatments, including immune checkpoint inhibitors (ICIs) and intravesical immunotherapy, represent major clinical hurdles. Synthesizing emerging evidence on the gut–tumor axis shows how the gut, urobiome, and intratumoral microbiota (IM) collectively influence the tumor microenvironment (TME) and therapeutic outcomes. This influence extends beyond chronic inflammation and direct genotoxicity to include metabolic crosstalk that shapes the host immune landscape. The composition of the gut microbiota is emerging as a potential predictive marker for ICI efficacy, as the enrichment of certain beneficial taxa has been linked to favorable outcomes. Microbial metabolic pathways are also implicated in therapeutic resistance; microbial metabolism of host hormonal precursors is hypothesized as one mechanism contributing to resistance to endocrine therapies. Furthermore, systemic and local communities may interact, wherein gut-derived metabolites can enhance systemic immunotherapy, while the local urobiome may interfere with intravesical treatment efficacy. However, clinical translation faces major impediments. A primary challenge is the lack of methodological standardization, which generates observational inconsistencies and complicates causal inference. Future progress will therefore depend on large-scale, longitudinal, multiomics clinical trials using harmonized protocols. This review provides a comparative narrative synthesis of shared and distinct mechanisms across the three major urological cancers and outlines priorities for future interventions and precision medicine in urologic oncology.</p>

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Microbiota-mediated modulation of the tumor microenvironment in urological cancers: crosstalk between gut and intratumoral microbiota

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Zhibiao Li,
  • Haoxiang Xu,
  • Lin Yang,
  • Jun Zheng,
  • Weijia Li,
  • Rulin Liao,
  • Wenxue Huang,
  • Boyuan Sun,
  • Zhuohang Li,
  • Cunzhen Ma,
  • Xunguo Yang,
  • Peidan Peng,
  • Jie Zhao,
  • Bisheng Cheng,
  • Peng Wu

摘要

Recent studies indicate the gut microbiome as a crucial regulator of cancer therapy, yet its role in urological malignancies remains incompletely understood. High rates of resistance to cornerstone treatments, including immune checkpoint inhibitors (ICIs) and intravesical immunotherapy, represent major clinical hurdles. Synthesizing emerging evidence on the gut–tumor axis shows how the gut, urobiome, and intratumoral microbiota (IM) collectively influence the tumor microenvironment (TME) and therapeutic outcomes. This influence extends beyond chronic inflammation and direct genotoxicity to include metabolic crosstalk that shapes the host immune landscape. The composition of the gut microbiota is emerging as a potential predictive marker for ICI efficacy, as the enrichment of certain beneficial taxa has been linked to favorable outcomes. Microbial metabolic pathways are also implicated in therapeutic resistance; microbial metabolism of host hormonal precursors is hypothesized as one mechanism contributing to resistance to endocrine therapies. Furthermore, systemic and local communities may interact, wherein gut-derived metabolites can enhance systemic immunotherapy, while the local urobiome may interfere with intravesical treatment efficacy. However, clinical translation faces major impediments. A primary challenge is the lack of methodological standardization, which generates observational inconsistencies and complicates causal inference. Future progress will therefore depend on large-scale, longitudinal, multiomics clinical trials using harmonized protocols. This review provides a comparative narrative synthesis of shared and distinct mechanisms across the three major urological cancers and outlines priorities for future interventions and precision medicine in urologic oncology.