This facilitates the translocation of microbial products such as LPS and trimethylamine N-oxide (TMAO), which return to the liver, perpetuating hepatic injury and fibrosis.290,291 Bile acid receptors, farnesoid X receptor (FXR) and TGR5, mediate this feedback loop; FXR activation bolsters barrier integrity and GLP-1 secretion, whereas TGR5 curbs inflammation via cAMP signaling—both of which are compromised in liver disease states such as primary sclerosing cholangitis (PSC).292. This evidence concerns the gene NR1H4 and sclerosing cholangitis.