Fig. 3

The mechanisms by which the gut microbiota promotes CRC metastasis by targeting the secondary soil. E. coli can directly open the GVB through a TTSS Virf-dependent mechanism and translocate into the liver, where it initiates the recruitment of macrophages, neutrophils, and inflammatory monocytes, which promotes PMN maturation and favors mCRC formation. F. nucleatum significantly increases plasma levels of pro-inflammatory cytokines as well as modulates liver immune responses, including the recruitment of MDSCs, decreased infiltration of NK cells and Th17 cells, and increased accumulation of regulatory T cells. The combination of Fap2 protein of F. nucleatum and NK Cell receptor, T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), can protect tumours from NK cells attack, thus benefiting the survival of CRC cells. F. nucleatum increases the expression of MDSCs to inhibit CD4⁺ T cells. All these mechanisms result in CRLM. The Figure was created with BioRender.com.

Abbreviations: CRLM, colorectal cancer liver metastasis; E. coli, Escherichia coli; F. nucleatum, Fusobacterium nucleatum; GVB, gut vascular barrier; mCRC, metastatic colorectal cancer; MDSCs, myeloid-derived suppressor cells; NK, natural killer; PMN, pre-metastatic niche; Th17, T helper-17; TTSS, type III secretion system; Virf, virulence factor