Publications by authors named "E Distrutti"
Background And Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterised by progressive biliary inflammation and fibrosis, leading to liver cirrhosis and cholangiocarcinoma. GPBAR1 (TGR5) is a G protein-coupled receptor for secondary bile acids. In this study, we have examined the therapeutic potential of BAR501, a selective GPBAR1 agonist in a PSC model.
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- The dysbiotic gut microbiota and bile acids play a crucial role in the immune dysfunction seen in inflammatory bowel disease (IBD), as shown by changes in bile acid excretion and gut microbiota composition.
- Elevated primary bile acids and reduced secondary bile acids were linked to increased disease severity and inflammatory responses in IBD patients and murine colitis models.
- The study identified five specific bile acids that, when administered, could reverse colitis and intestinal dysbiosis, suggesting the potential for treatments targeting bile acid profiles in managing IBD.
Article Synopsis
- - Primary sclerosing cholangitis (PSC) is a rare chronic liver disease with no approved treatments; currently, ursodeoxycholic acid (UDCA) is used, but it doesn't improve survival or delay liver transplants.
- - A range of new potential drugs is being developed, mainly focusing on FXR agonists like obeticholic acid, as well as other agents targeting bile acid metabolism and cholangiocyte function.
- - Additional therapies under investigation include drugs that target gut bacteria, PPARs, anti-itching agents, and immunosuppressive medications, reflecting the connection between PSC and gut microbiota.
Article Synopsis
- Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease that, if left untreated, can lead to severe liver damage, including cirrhosis, and may require a transplant.
- The disease is influenced by genetic factors and specific environmental triggers, with an imbalance in gut microbiota (dysbiosis) being a significant factor.
- Current treatments include bile acid-based therapies like ursodeoxycholic acid, but new therapies such as elafibranor and seladelpar are being explored to enhance treatment options and personalize care for patients.
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic disorders characterized by dysregulated immune response and persistent inflammation. Recent studies suggest that bile acid receptors, particularly GPBAR1, and the transcription factor RORγt play critical roles in modulating intestinal inflammation. This study evaluates the therapeutic potential of PBT002, a dual GPBAR1 agonist and RORγt inverse agonist, in IBD models.
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