Table 1 Mechanisms by which the gut microbiota remolds TME to promote CRC metastasis in different ways
From: Role of imbalanced gut microbiota in promoting CRC metastasis: from theory to clinical application
Microbiota | Result | Mechanism | Experimental method | References |
|---|---|---|---|---|
F. nucleatum | recruit tumour-infiltrating immune cells | F. nucleatum can recruit MDSCs and TAMs in TME, causing a decrease in CD8+ T cell density to suppress immunity in CRC patients, thereby promoting CRC metastasis. | in vitro | [61] |
F. nucleatum induces the expression of the DAMP molecule S100A9 in CRC cells and subsequent M2 macrophage polarization via activating the TLR4/NF-κB signaling pathway. | in vitro | [66] | ||
F. nucleatum infection activates the IL-6/p-STAT3/c-MYC signaling pathway in a TLR4-dependent way to increase M2 macrophage polarization and promote CRC growth and metastasis. | in vitro and in vivo | [67] | ||
F. nucleatum promotes macrophage infiltration through activation of the chemokine CCL20, and induces M2 macrophage polarization, enhancing CRC metastasis. | in vitro | [74] | ||
promote cell adhesion | F. nucleatum can promote adhesion of CRC cells to endothelial cells by inducing the ALPK1/NF-κB/ICAM1 axis, thus promoting extravasation and metastasis. | in vitro and in vivo | [68] | |
induce the secretion of pre-metastatic cytokines | F. nucleatum drives metastasis by selectively inducing pro-inflammatory and pro-metastatic cytokines IL-8 and CXCL1 from CRC cells via the bacterial surface adhesin Fap2. | in vitro | [75] | |
F. nucleatum binds to the E-cadherin receptor to cause the activation of β-catenin and stimulates the expression of pro-inflammatory cytokines. | in vivo | [76] | ||
regulate tumour metabolism | F. nucleatum nucleatum increases CRC glycolysis by targeting the lncRNA ENO1-IT1 and the KAT7 histone modification axis, which is an important promoter of CRC metastasis. | in vitro and in vivo | ||
ETBF | recruit tumour-infiltrating immune cells | ETBF promotes M2 polarization of macrophages, and M2 macrophages can promote CRC metastasis via their secreted proteins and/or regulatory factors. | in vitro | [79] |
The combined effect of BFT and IL-17 on colonic epithelial cells promotes the differentiation of MO-MDSCs that selectively upregulate Arg1 and Nos2 to producing NO, inhibiting T cell proliferation. | in vivo | [80] | ||
E. coli | recruit tumour-infiltrating immune cells | E. coli stimulates the secretion of CTSK, which can bind to TLR4, stimulating M2 polarization of TAMs through an mTOR-dependent pathway and promoting CRC metastasis through the NF-κB pathway. | in vitro and in vivo | [81] |