Lipid accumulation inhibition strategies alleviate Fusobacterium nucleatum-infected colorectal cancer

作者：Zhongkun Zhou, Yuqing Niu, Yunhao Ma, Dekui Zhang, Yiqing Wang, Rui Ji, Jianfang Zhao, Chi Ma, Hongmei Zhu, Ying‐Qian Liu, Lixue Tu, Juan Lu, Baizhuo Zhang, Hua Zhang, Xin Ma, Peng Chen · 发表于：Microbiome · 年份：2025 · DOI：10.1186/s40168-025-02133-7 · 被引用次数：11 · 研究领域：Gut microbiota and health、Probiotics and Fermented Foods、Cancer Research and Treatments

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is prevalent in colorectal cancer (CRC), and it can promote proliferation and induce chemoresistance via multiple pathways. The development of treatment strategies for F. nucleatum-infected CRC is of great importance. METHODS: Shotgun metagenomic and metabolomic analyses of human feces, as well as metabolomic analysis of human blood, were performed to reveal the dysbiosis and metabolic dysregulation in CRC. Furthermore, the effects of Bifidobacterium animalis (B. animalis) on F. nucleatum and CRC were assessed in vitro and in vivo. Using a mouse CRC model, the function of bile salt hydrolase (BSH) in B. animalis was verified through heterologous expression in Escherichia coli (E. coli). Bile acids and drug library screening experiments were performed to inhibit F. nucleatum and tumor proliferation. RESULTS: We identified an increase in F. nucleatum, enrichment of lipid metabolites, and depletion of Bifidobacterium in CRC patients. Furthermore, B. animalis inhibited F. nucleatum and CRC cells growth in an acid-dependent manner and reduced F. nucleatum-induced tumor increasement in mice. Mechanistically, F. nucleatum caused lipid accumulation, exacerbated inflammation, and intestinal barrier disruption, whereas B. animalis alleviated these changes, increased the Simpson diversity index, reduced lipid metabolites, and altered secondary bile acid composition in mice. Moreover, E. coli-BSH and ursodeoxycholic acid (UDCA) inhibited...