Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease

Abstract

Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common gastroenterological emergency associated with significant morbidity and mortality. Gastroenterologists and other involved clinicians are generally assisted by international guidelines in its management. However, NVUGIB due to peptic ulcer disease only is mainly addressed by current guidelines, with upper gastrointestinal endoscopy being recommended as the gold standard modality for both diagnosis and treatment. Conversely, the management of rare and extraordinary rare causes of NVUGIB is not covered by current guidelines. Given they are frequently life-threatening conditions, all the involved clinicians, that is emergency physicians, diagnostic and interventional radiologists, surgeons, in addition obviously to gastroenterologists, should be aware of and familiar with their management. Indeed, they typically require a prompt diagnosis and treatment, engaging a dedicated, patient-tailored, multidisciplinary team approach. The aim of our review was to extensively summarize the current evidence with regard to the management of rare and extraordinary rare causes of NVUGIB.

Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy

“…Tightly controlling the enzymes and transporters involved in BA synthesis is critical for BA homeostasis and is mediated by BA signaling [ 32 ]. BAs bind to receptors and activate the downstream signaling pathways [ 33 , 34 ]. FXR is a nuclear receptor that is highly expressed in enterocytes and hepatocytes.…”

“…FXR is a nuclear receptor that is highly expressed in enterocytes and hepatocytes. It is involved in the regulation of BA synthesis, uptake, secretion, and detoxification, regulating intestinal FGF15/19 signaling and immune response via the inhibition of NF-kB in the liver and intestine [ 33 , 34 , 35 , 36 ]. CDCA has the highest affinity for FXR receptor binding, followed by DCA, LCA, and CA [ 34 ].…”

“…It is involved in the regulation of BA synthesis, uptake, secretion, and detoxification, regulating intestinal FGF15/19 signaling and immune response via the inhibition of NF-kB in the liver and intestine [ 33 , 34 , 35 , 36 ]. CDCA has the highest affinity for FXR receptor binding, followed by DCA, LCA, and CA [ 34 ]. TGR5 is a membrane-bound receptor expressed in the epithelial cells, immune cells, and intestinal nerves in the gut and biliary tract [ 33 , 34 ].…”

“…CDCA has the highest affinity for FXR receptor binding, followed by DCA, LCA, and CA [ 34 ]. TGR5 is a membrane-bound receptor expressed in the epithelial cells, immune cells, and intestinal nerves in the gut and biliary tract [ 33 , 34 ]. It plays a role in inhibiting the pro-inflammatory function of macrophages by downregulating TLR4-mediated NF-kB signaling, as well as glucose-metabolism-related functions [ 33 , 34 , 37 , 38 ].…”

“…TGR5 is a membrane-bound receptor expressed in the epithelial cells, immune cells, and intestinal nerves in the gut and biliary tract [ 33 , 34 ]. It plays a role in inhibiting the pro-inflammatory function of macrophages by downregulating TLR4-mediated NF-kB signaling, as well as glucose-metabolism-related functions [ 33 , 34 , 37 , 38 ]. LCA is the most potent agonist of TGR5, followed by DCA, CDCA, and CA [ 34 ].…”