Journal of Translational Medicine · Published 2026-07-29 · DOI 10.1186/s12967-026-08731-9
Wenpei Shi, Na Li, Shanshan Cheng, Yaqian Zhao, Yue Zhang, Hui Ding, Yi Li, Ruomeng Bi, Xinyu Lu, Zhen Li, Yu Wang
Abstract 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.
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Shi, W., Li, N., Cheng, S., et al. (2026). Chemotherapy-driven gut microbiota remodeling in ovarian cancer: a prospective longitudinal study. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-08731-9