Table 2.

Factors promoting CRC

Origins	Products	Potential microbe	Mechanism	References
BA	DCA and LCA	Clostridium, Enterococcus, Bifidobacterium, Lactobacillus	produce ROS and RNS, causing oxidative stress, and damaging DNA	69
			K-ras point mutual mutations	70
			Stimulate EGFR-MARK signaling	70
			Regulate M3R and Wnt/β-catenin signaling	78
Choline and phospholipids	TMAO	Unknown	Promotes inflammation	87
Sulfates and other sulfur-containing compounds	H2S	Sulfate-reducing bacteria	Promotes inflammation, genotoxicity, inhibits butyric acid oxidation	93–96
Bacterial toxins	B.fragilis toxin (BFT)	Enterotoxigenic bacteria fragilis (ETBF)	Induces E-cadherin lysis, resulting in loss of epithelial integrity	105
			Triggers activation of Wnt, induces c-Myc expression and promotes CEC proliferation	106
			Activates NF-κB signaling and promotes inflammation	107
			Upregulates the expression of SMOX genes, leading to DNA damage	108,109
			Activates Stat3 to regulate Th17 cells and maintain NF-κB activity	112,116
	FadA	Fusobacterium nucleatum (Fn)	Binds to CDH5, increases endothelial permeability, and allows bacteria to pass through loose junctions	117
			Binds to E-cadherin and mediates Fn adhesion and invasion of CRC cells	117
			Binding to E-cadherin inhibits its tumor suppressor activity and increases the expression of NF-κB and Wnt pathways	121
	Colibactin	E. coli and other gram-negative bacteria	Leads to double-stranded DNA breaks, chromosomal instability and cellular senescence	122,126–128
	Cytolethal distending toxin (CDT)		Causes DNA damage, leading to cell cycle arrest and cellular senescence or death	133–135

CRC: colorectal cancer

BA: bile acids

DCA: deoxycholic acid

LCA: lithocholic acid

ROS: reactive oxygen species

RNS: reactive nitrogen substances

EGFR: epidermal growth factor receptor

MAPK: mitogen activated protein kinase

TMAO: trimethylamine n-oxide

H2S: Hydrogen sulfide

BFT: fragile bacteroides toxin

ETBF: enterotoxigenic fragile bacteroides

CEC: colonic epithelial cells

SMOX: spermine oxidase

NF-κB: NF-kappaB

Fn: Fusobacterium nucleatum

CDT: cytolethal distending toxin