Research Paper Volume 14, Issue 4 pp 1941—1958

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

Han Yin1, , Zhuangzhuang Miao2, , Lu Wang1, , Beibei Su1, , Chaofan Liu1, , Yu Jin1, , Bili Wu1, , Hu Han1, , Xianglin Yuan1, ,

  • 1 Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
  • 2 Department of Neurosurgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

Received: September 17, 2021       Accepted: December 11, 2021       Published: February 25, 2022
How to Cite

Copyright: © 2022 Yin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 Fusobacterium nucleatum (F.nucleatum) to the microbiota-liver axis of CRC in mice, focusing on the correlation between liver immunity and gut microbiota alterations. When F. nucleatum 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 F. nucleatum 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 F. nucleatum exposure abridged the murine gut microbiota diversity, inducing an imbalanced and restructured intestinal microflora. In particular, the abundance of CRC-promoting bacteria such as Enterococcus and Escherichia/Shigella was evidently elevated post F. nucleatum treatment. Thus, our findings suggest that F. nucleatum 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.


CRC: Colorectal cancer; CRLM: Colorectal cancer liver metastasis; MDSC: Myeloid-derived suppressor cells; NK: Natural killer; TNFα: Tumor necrosis factor alpha; IFN-γ: Interferon-gamma; MCP-1: Macrophage chemoattractant protein-1; CXCL1: chemokine (C-X-C motif) ligand 1; TAM: Tumor-associated macrophage; CGMCC: The China General Microbiological Culture Collection Center; ROI: Region of interest; RDP: Ribosomal Database Program; PCoA: Principal Co-ordinate Analysis; NMDS: Non-metric Multidimensional Scaling; LDA: Linear Discriminant Analysis; LEfSe: Linear Discriminant Analysis Effect Size; LPS: Lipopolysaccharides.