Scholarlink

Background <p>The gut microbiome shapes chemotherapy efficacy and outcomes in several cancers, but evidence in ovarian cancer (OC) remains limited and largely cross-sectional. Despite high initial response rates, long-term relapse in OC remains frequent, while conventional markers capture only short-term therapeutic sensitivity. Whether longitudinal gut-microbiome trajectories during chemotherapy are associated with long-term recurrence remains unknown.</p> Methods <p>Within the prospective SOCFCP cohort (<i>N</i> = 91; 13 recurrences), 100 serial fecal samples from a 33-patient sub-cohort were analyzed by 16S rRNA sequencing across the early, middle and late chemotherapy phases. Microbial successional trajectories and their association with recurrence were assessed by linear mixed-effects modeling, multivariable MaAsLin3 and repeated-measures correlation (rmcorr) networks, alongside stratified and covariate-adjusted sensitivity analyses and patient-level bootstrap assessment. The cumulative severe-toxicity–recurrence relationship was estimated by Firth penalized-likelihood regression, suited to sparse, separation-prone events.</p> Results <p>Microbial α-diversity rose progressively across the chemotherapy course (Shannon time effect <i>p</i> = 0.002), consistent with ecological succession, with higher turnover among peripheral than in core taxa (<i>p</i> = 0.005). Cumulative severe toxicity was not associated with recurrence (Firth OR = 0.99, 95% CI 0.68–1.39). Crucially, recurrent patients exhibited a progressive depletion of <i>Fusicatenibacter</i> (recurrence × time coefficient = −5.35, <i>q</i> &lt; 0.001) that persisted across all sensitivity analyses—stratified, medication-adjusted, antibiotic-depleted and clinically-adjusted models (coefficient −4.60 to −5.66, all <i>q</i> &lt; 0.001). PICRUSt2-based functional inference identified recurrence-associated differences in predicted de novo nucleotide-biosynthesis and cell-wall-assembly pathway abundance (<i>q</i> &lt; 0.05). A bootstrap-supported co-variation network further linked specific taxa, notably <i>Escherichia-Shigella</i> and <i>Roseburia</i>, to these recurrence-associated pathways.</p> Conclusion <p>Chemotherapy-driven gut-microbiome remodeling, in particular the recurrence-associated depletion of <i>Fusicatenibacter</i>, was associated with long-term OC relapse, whereas cumulative severe toxicity showed no significant association with recurrence. These longitudinal microbial dynamics support a candidate non-invasive marker that warrants external validation, and provide a hypothesis-generating rationale for testing whether targeting specific predicted bacterial functional pathways can modulate the host anti-tumor milieu.</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

Chemotherapy-driven gut microbiota remodeling in ovarian cancer: a prospective longitudinal study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月29日

查看全文
  • Wenpei Shi,
  • Na Li,
  • Shanshan Cheng,
  • Yaqian Zhao,
  • Yue Zhang,
  • Hui Ding,
  • Yi Li,
  • Ruomeng Bi,
  • Xinyu Lu,
  • Zhen Li,
  • Yu Wang

摘要

Background

The gut microbiome shapes chemotherapy efficacy and outcomes in several cancers, but evidence in ovarian cancer (OC) remains limited and largely cross-sectional. Despite high initial response rates, long-term relapse in OC remains frequent, while conventional markers capture only short-term therapeutic sensitivity. Whether longitudinal gut-microbiome trajectories during chemotherapy are associated with long-term recurrence remains unknown.

Methods

Within the prospective SOCFCP cohort (N = 91; 13 recurrences), 100 serial fecal samples from a 33-patient sub-cohort were analyzed by 16S rRNA sequencing across the early, middle and late chemotherapy phases. Microbial successional trajectories and their association with recurrence were assessed by linear mixed-effects modeling, multivariable MaAsLin3 and repeated-measures correlation (rmcorr) networks, alongside stratified and covariate-adjusted sensitivity analyses and patient-level bootstrap assessment. The cumulative severe-toxicity–recurrence relationship was estimated by Firth penalized-likelihood regression, suited to sparse, separation-prone events.

Results

Microbial α-diversity rose progressively across the chemotherapy course (Shannon time effect p = 0.002), consistent with ecological succession, with higher turnover among peripheral than in core taxa (p = 0.005). Cumulative severe toxicity was not associated with recurrence (Firth OR = 0.99, 95% CI 0.68–1.39). Crucially, recurrent patients exhibited a progressive depletion of Fusicatenibacter (recurrence × time coefficient = −5.35, q < 0.001) that persisted across all sensitivity analyses—stratified, medication-adjusted, antibiotic-depleted and clinically-adjusted models (coefficient −4.60 to −5.66, all q < 0.001). PICRUSt2-based functional inference identified recurrence-associated differences in predicted de novo nucleotide-biosynthesis and cell-wall-assembly pathway abundance (q < 0.05). A bootstrap-supported co-variation network further linked specific taxa, notably Escherichia-Shigella and Roseburia, to these recurrence-associated pathways.

Conclusion

Chemotherapy-driven gut-microbiome remodeling, in particular the recurrence-associated depletion of Fusicatenibacter, was associated with long-term OC relapse, whereas cumulative severe toxicity showed no significant association with recurrence. These longitudinal microbial dynamics support a candidate non-invasive marker that warrants external validation, and provide a hypothesis-generating rationale for testing whether targeting specific predicted bacterial functional pathways can modulate the host anti-tumor milieu.