Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota

• Published in: Aging (Albany, NY.) NY.), 2022-02, Vol.14 (4), p.1941-1958
• Main Authors: Yin, Han, Miao, Zhuangzhuang, Wang, Lu, Su, Beibei, Liu, Chaofan, Jin, Yu, Wu, Bili, Han, Hu, Yuan, Xianglin
• Format: Article
• Language: English
• Subjects: Animals; Colorectal Neoplasms - pathology; Cytokines; Fusobacterium Infections - complications; Fusobacterium Infections - microbiology; Fusobacterium Infections - pathology; Fusobacterium nucleatum; Gastrointestinal Microbiome; Humans; Liver Neoplasms - complications; Mice; Research Paper
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.203914

Liver metastasis is the major cause of death in colorectal cancer (CRC) patients. Nevertheless, the underlying mechanisms remain unknown. Gut microbiota intricately affect the initiation and progression of CRC by instigating immune response through the secretion of pro-inflammatory cytokines. In this study, we investigated the contribution of to the microbiota-liver axis of CRC in mice, focusing on the correlation between liver immunity and gut microbiota alterations. When was orally administered to mice, CRC liver metastasis was evidently exaggerated and accompanied by noticeable deleterious effects on body weight, cecum weight, and overall survival time. Further evaluation of the immune response and cytokine profiles revealed a substantial increase in the levels of pro-inflammatory cytokines such as IL6, IL12, IL9, IL17A, CXCL1, MCP-1, TNF-α, and IFN-γ in the plasma of mice treated with as compared to that in the untreated control mice. Besides, hepatic immune response was also modulated by recruitment of myeloid-derived suppressor cells, reduction in the infiltration of natural killer (NK) and T helper-17 (Th17) cells, as well as increase in regulatory T cell accumulation in the liver. Additionally, sustained exposure abridged the murine gut microbiota diversity, inducing an imbalanced and restructured intestinal microflora. In particular, the abundance of CRC-promoting bacteria such as and was evidently elevated post treatment Thus, our findings suggest that might be an important factor involved in promoting CRC liver metastasis by triggering of liver immunity through the regulation of gut microbiota structure and composition.