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FXR activation inhibits inflammation and preserves the intestinal barrier in IBD
  1. Manon E Wildenberg1,2,
  2. Gijs R van den Brink1,3
  1. 1Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands
  2. 2Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands
  3. 3Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
  1. Correspondence to Gijs R van den Brink, Academic Medical Center, C2, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; g.r.vandenbrink{at}amc.nl

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Bile salts are produced in the liver and delivered to the duodenum, where they emulsify lipids to facilitate absorption. After passing through the small intestine, the majority of bile salts are reabsorbed for recycling in the terminal ileum. One of the key receptors involved in this reabsorption is the farnesoid X receptor (FXR), a member of the family of nuclear receptors which function as transcription factors. FXR signalling regulates target genes involved in bile acid synthesis (CYP7a), efflux (ABCB11) and absorption of conjugated bile acids (IBABP).

In line with the role of FXR in bile homeostasis, FXR–/– mice were initially described to have aberrancies in bile acid and lipid homeostasis, with elevated cholesterol levels in both liver and serum.1 Interestingly, when these animals were followed up for longer periods, hepatic levels of the proinflammatory cytokines interferon γ, interleukin 6 (IL-6) and tumour necrosis factor α (TNFα) were increased, suggesting an additional role for FXR in immunoregulation.2 This role was further confirmed in ApoE–/– mice, which develop aortic plaques after being fed a high-cholesterol diet. Administration of an FXR agonist reduced plaque formation as well as intraplaque expression of inflammatory mediators, supporting an immunomodulatory …

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