Tumor-colonizing Bifidobacterium dentium promotes tumor progression and chemotherapy resistance via MMP3 and GABA-FOXA2-P-gp axis.

Authors

Xiaoyun Pan, Shuyi Luo, Shuheng Dou, Yiqiu Li, Chanci Qiu, Qiao Pan, Xiaoshi Zhang, Ge Zhang, Songhe Guo

Published in

Cell reports. Medicine. Pages 103142. Nov 09, 2026. Epub Nov 09, 2026.

Abstract

The intratumoral microbiota plays a crucial role in cancer pathogenesis; however, the specific members involved and their mechanisms remain incompletely defined. Here, we identify Bifidobacterium dentium (B. dentium ) as a tumor-associated bacterium enriched in fecal samples from patients with melanoma and colorectal cancer (CRC) and detectable in human melanoma and CRC tissues. High intratumoral B. dentium abundance correlates with poorer survival in CRC patients. In mouse models, subgingival administration of live B. dentium enables tumor homing and accelerated CT26 and B16F10 tumor growth, including in an orthotopic CT26 colorectal tumor model. Mechanistically, B. dentium invades tumor cells, promotes proliferation through Akt/ERK activation, enhances metastatic potential through MMP3 induction, and increases resistance to key chemotherapeutic agents. B. dentium-derived GABA activates FOXA2-dependent P-gp upregulation, contributing to chemotherapy resistance. These findings establish B. dentium as a niche-dependent pro-tumoral pathobiont and a potential target for improving cancer treatment response.

PMID:
43003090
Bibliographic data and abstract were imported from PubMed on 10 Nov 2026.

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