_Hlk491099574

Abstract | Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the li

Key points

Enterohepatic circulation of bile acids

Figure 1 | Bile acid biosynthesis, transport and metabolism. The most abundant bile acids (BAs) in mammals include the primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and the secondary BAs deoxycholic acid (DCA) and lithocholic acid (LCA). B

Signalling by bile acids

Figure 2 | Enterohepatic circulation of bile acids under normal physiological conditions and during dysbiosis and inflammation. The enterohepatic circulation of bile acids (BAs) between the intestine (enterocytes) and liver (hepatocytes) under normal phys

Bile acids, liver inflammation and HCC

Figure 3 | Bile acid-induced hepatic inflammation and carcinogenesis. Due to their lipophilic, detergent properties, bile acids (BAs) can directly disrupt the plasma membrane and cause activation of protein kinase C (PKC), which then activates the p38 mit

Bile acids, colon inflammation and CRC

Figure 4 | Bile-acid-induced TGR5 signalling pathways in macrophages. The M1 macrophage phenotype is pro-inflammatory, and the M2 phenotype is immunosuppressive. Although bile acids (BAs) are not able to induce complete macrophage polarization to either t

Figure 5 | Effects of intestinal bile acids on colorectal carcinogenesis. Secondary bile acids (BAs), in particular deoxycholic acid (DCA), influence several signalling pathways in enterocytes that can lead to the development of colorectal cancer (CRC). B

Targeting bile acid signalling

Table 1 | Clinical trials and ongoing studies targeting bile acid signalling in gastrointestinal diseases

Conclusions