Gut microbiota dynamics during chemotherapy in epithelial ovarian cancer patients are related to therapeutic outcome

Epithelial ovarian cancer (EOC) is one of the most lethal and silent gynecological tumors. Despite appropriate surgery and chemotherapy, relapse occurs in over half of patients with a poor prognosis. Recently, the gut microbiota (GM) has been hypothesized to influence the efficacy of anticancer therapies, but no data are available in EOC. Here, by 16S rDNA sequencing and inferred metagenomics, we profiled the GM of EOC patients at diagnosis and reconstructed its trajectory, along the course of neoadjuvant or adjuvant chemotherapy up to follow-up. Compared to healthy subjects, the GM of EOC patients was dysbiotic and severely affected by chemotherapy. Strikingly, discriminating patterns were identified in relation to the therapeutic response. Platinum-resistant patients showed a marked temporal reduction in GM diversity and increased instability, with loss of health-associated taxa and increased proportions of Coriobacteriaceae and Bifidobacterium. Notably, most of these microorganisms are lactate producers, suggesting increased lactate production, as supported by inferred metagenomics. In contrast, the GM of platinum-sensitive patients appeared overall more diverse and stable, and enriched in lactate utilizers from the Veillonellaceae family. In conclusion, we identified potential GM signatures of therapeutic outcome in EOC patients, which could open up new opportunities for cancer prognosis and treatment.

上皮性卵巢癌（Epithelial Ovarian Cancer, EOC）是致死性最强且最为隐匿的妇科肿瘤之一。尽管接受规范手术与化疗，仍有超半数患者会出现复发且预后不良。近年来，肠道菌群（Gut Microbiota, GM）被认为可影响抗癌治疗的疗效，但目前尚无针对上皮性卵巢癌的相关研究数据。本研究通过16S rDNA测序与推断宏基因组学技术，对确诊时的上皮性卵巢癌患者的肠道菌群进行了特征解析，并重建了其在新辅助化疗或辅助化疗直至随访阶段的动态变化轨迹。与健康受试者相比，上皮性卵巢癌患者的肠道菌群存在失调，且受化疗影响显著。值得注意的是，研究团队识别出与治疗应答相关的特征性菌群模式：铂耐药患者的肠道菌群多样性随时间显著降低，菌群不稳定性升高，同时伴随健康相关菌群类群的丢失，以及科里杆菌科（Coriobacteriaceae）和双歧杆菌属（Bifidobacterium）的相对丰度升高。值得关注的是，上述多数菌群均为乳酸产生菌，提示乳酸生成增加，这一结论得到了推断宏基因组学分析的支持。与之相反，铂敏感患者的肠道菌群整体多样性更高、稳定性更强，且富集了韦荣球菌科（Veillonellaceae）中的乳酸利用菌。综上，本研究鉴定出上皮性卵巢癌患者治疗结局的潜在肠道菌群特征谱，可为癌症预后评估与治疗策略优化提供新的思路。