Researchers discovered that therapies targeting the signaling of bile acids represent a promising and effective strategy to treat complex liver disorders, as published in Biomedicine & Pharmacotherapy.
The incidence of liver disease has risen sharply over the last few years. Liver disease encompasses a wide range of diagnoses, from nonalcoholic fatty liver disease to hepatitis to Alagille syndrome (ALGS). Although liver diseases may have entirely different etiologies, they mostly share pathophysiological mechanisms that are linked to the imbalance of bile acid homeostasis.
“Bile acids have emerged as critical signaling molecules participating in energy, lipid and glucose metabolism, cell proliferation, detoxification reactions, as well as the regulation of the immune system,” the authors of the study wrote.
Read more about ALGS etiology
The dysregulation of bile acid expression and distribution commonly observed in a wide range of liver diseases suggests that it may represent a potential therapeutic target. The authors of this study conducted a literature review to summarise the development of therapies that modulate bile duct signaling in the gut-liver axis.
They reported that there has been a considerable emergence of novel therapies targeting bile acids and associated signaling pathways in recent years. Among the therapies that have shown promise are FGF19 analogs, ASBT inhibitors, and TGR5 agonists.
Studies investigating the role of bile acids in regulating liver diseases confirm that bile acids play an important role in immune homeostasis. In addition, bile acids have been shown to play a role in regulating the composition of gut microbiota, which in turn plays a role in the pathogenesis of many liver diseases. These findings demonstrate why the targeting of bile acids has therapeutic potential.
“Liver diseases are still leading public health concerns, so effective treatment strategies are urgently needed,” the authors concluded. “We believe that pharmacological therapies targeting [bile acid] signaling are promising and efficient strategies for the treatment of liver diseases, including both metabolic diseases and cholangiopathies.”
Duan S, Li X, Fan G, Liu R. Targeting bile acid signaling for the treatment of liver diseases: from bench to bed. Biomed Pharmacother. 2022;152:113154. doi:10.1016/j.biopha.2022.113154