Veillonella Associates with Platinum Resistance in Ovarian Cancer: Insights from Gut Microbiota Profiling and In Vitro Functional Validation

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Abstract

Background Ovarian cancer (OC) remains the most lethal gynecologic malignancy, primarily due to high recurrence rates and frequent development of platinum resistance. While the gut microbiome is known to influence tumor progression and therapeutic response, its role in extraintestinal malignancies like OC remains poorly understood. Methods We collected fecal samples from six platinum-sensitive and three platinum-resistant OC patients. Clinical data were collected, and gut microbiota profiles were assessed using metagenomic next-generation sequencing (mNGS). Differentially abundant taxa were determined through linear discriminant analysis effect size (LEfSe). Functional profiling was conducted with STAMP, and correlations with clinical variables were assessed using the R “psych” package. The effects of Veillonella , the most resistance-associated species, on ovarian cancer cell behavior were validated in vitro. Results Compared to the sensitive group, resistant patients demonstrated a marked depletion of beneficial commensals such as Bacteroides and Faecalibacterium , alongside an overrepresentation of Firmicutes -affiliated taxa. Notably, Veillonella abundance was significantly positively correlated with platinum resistance (p < 0.05). Functional experiments demonstrated that Veillonella promoted ovarian cancer cell proliferation, motility, invasiveness, and resistance to chemotherapy. Conclusion Our findings suggest that the fecal microbiome, particularly Veillonella , may serve as a potential biomarker for assessing platinum sensitivity in OC and provide new insights into the microbiota-mediated mechanisms of chemoresistance.

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