Table 4.

Role of gut bacteria-derived bile acid metabolites in tumorigenesis.

Gut bacteria-derived bile acids and SCFAs	Mechanism involved in tumorigenesis	References
LCA	Induces the growth of colon cancer Activates VDR gene expression which induces the alterations of gut microbiota such as the lower abundance of Lactobacillus and higher abundance of Clostridium and Bacteroides which drive the progression of CRC	[14]
DCA	Induces proliferation and invasion of colon cancer cells through activation of COX-2, epidermal growth factor receptor (EGFR), extracellular signal-regulated kinases 1 and 2 (ERK1/2), activator protein 1 (AP1), c-Myc, and NF-kB at very low concentration Induces the growth of opportunistic bacteria such as Desulfovibrio, Dorea, Escherichia-Shigella, and Ruminococcus as well as prevented the growth of beneficial bacteria such as Lactobacillus, Lactococcus, and Roseburia which drive the development of gastrointestinal cancer	[98] [99]
Cholic acid	Enhanced the abundance of opportunistic gut bacteria such as Prevotella and Desulfovibrio whereas reduced the abundance of Ruminococcus, Lactobacillus, and Roseburia which drive gastrointestinal tumorigenesis through overproduction of toxic substance DCA	[99]
DCA and LTA	Responsible for the development of liver cancer through inducing the synthesis of inflammatory cytokines (IL-6), chemokine (C-X-C motif) ligand (CXCL) 9, and prostaglandin E2 (PGE2)	[103]
	Induce overexpression of cyclooxygenase-2 (COX-2) and PGE2 that drive immune evasion of tumor cell by suppressing the activity of dendritic cells and natural killer T (NKT) cells; this induces the progression of hepatocellular carcinoma (HCC)	[104]
Chenodeoxycholic acid (CDCA)	Induces inflammation of HCT116 colon cancer cells through overexpression of COX-2	[107]
LCA and DCA (produced by BSH-rich bacterial genera such as Enterobacter, Enterococcus, and Clostridium)	Bind with GPBAR1 which induces colorectal cancer through activation of EGFR and STAT3 signaling, interaction between secondary bile acids and GPBAR1 is involved in controlling the activity of proinflammatory macrophages and anti-inflammatory macrophages Induce inflammation in the gastrointestinal tract through overexpression of NF-κB and proinflammatory cytokines such as TNF-α and IL-1β Induce activation of protein kinase C (PKC) which enhances the overexpression of NF-κB through activation of the p38 MAPK pathway; NF-κB induces the activation of inflammation through secretion of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6; IL-6 induces the development of HCC through activation of the JAK–STAT3 pathway and IL-1β enhances the survival of damaged DNA cells in HCC through activation of the phosphoinositide 3-kinase- (PI3K-) MDM2 pathway	[108] [4]