Intratumoral Collinsella aerofaciens exhibits antitumor activity in endometrial carcinoma through activation of the p53 signaling pathway.

BACKGROUND: The intratumoral microbiota plays dual roles in cancer progression and suppression, but its composition and functional mechanisms in endometrial carcinoma (EC) remain incompletely defined. This study aimed to characterize the EC intratumoral microbiome, elucidate microbial spatial localization, and identify bacteria with tumor-suppressive properties. METHODS: Tumor and adjacent normal tissues from patients with EC were analyzed using 5R 16S rRNA sequencing to profile microbial communities, with fluorescence in situ hybridization (FISH) validating bacterial localization. Spatial transcriptomics (ST), single-cell RNA sequencing (scRNA-seq), and FISH were integrated to map microbiota-niche cell interactions. RNA sequencing was performed on EC cells treated with bacterial supernatant. Fecal microbiota transplantation (FMT) from EC patients to mice was used to assess gut-tumor microbial crosstalk. RESULTS: Collinsella aerofaciens (C. aerofaciens), Haloamaerobium gallinarum, and Massilia oculi were enriched in adjacent normal tissues, while Bacteroides vulgatus (B. vulgatus) and Delfia tsuruhatensis dominated tumor tissues. Tumors exhibited reduced microbial richness versus normal tissues. C. aerofaciens localized predominantly to smooth muscle cells and modulated the tumor microenvironment, as revealed by FISH and ST-scRNA-seq integration. RNA sequencing suggested that C. aerofaciens suppressed EC progression by activating the p53 signaling pathway. FMT experiments demonstrated gut microbiota-driven remodeling of the tumor microbiome. CONCLUSIONS: This study identifies C. aerofaciens as a novel tumor-suppressive bacterium in EC, with mechanistic evidence linking its activity to p53 pathway activation. Gut microbiota modulates intratumoral microbial composition, suggesting potential dual-target therapeutic strategies for EC.