Intestinal Inflammation Alters the Expression of Hepatic Bile Acid Receptors Causing Liver Impairment.
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
15
5
2020
medline:
22
6
2021
entrez:
15
5
2020
Statut:
ppublish
Résumé
The gut-liver axis has been recently investigated in depth in relation to intestinal and hepatic diseases. Key actors are bile acid (BA) receptors, as farnesoid-X-receptor (FXR), pregnane-X-receptor (PXR), and G-protein-coupled-receptor (GPCR; TGR5), that control a broad range of metabolic processes as well as inflammation and fibrosis. The present study aims to investigate the impact of intestinal inflammation on liver health with a focus on FXR, PXR, and TGR5 expression. The strategy to improve liver health by reducing gut inflammation is also considered. Modulation of BA receptors in the inflamed colonic tissues of inflammatory bowel disease (IBD) pediatric patients is analyzed. A dextran sodium sulphate (DSS) colitis animal model was built. Co-cultures with Caco2 and HepG2 cell lines were set up. Modulation of BA receptors in biopsies of IBD pediatric patients was assessed by real-time PCR and immunohistochemistry. Histology showed inflammatory cell infiltration in the liver of DSS mice, where FXR and PXR were significantly decreased and oxidative stress was increased. Exposure of Caco2 to inflammatory stimuli resulted in the reduction of BA receptor expression in HepG2. Caco2 treatment with dipotassium glycyrrhizate (DPG) reduced these effects on liver cells. Inflamed colon of patients showed altered FXR, PXR, and TGR5 expression. This study strongly suggests that gut inflammation affects hepatic cells by altering BA receptor levels as well as increasing the production of pro-inflammatory cytokines and oxidative stress. Hence, reducing gut inflammation is needed not only to improve the intestinal disease but also to protect the liver.
Identifiants
pubmed: 32404746
doi: 10.1097/MPG.0000000000002759
pii: 00005176-202008000-00012
doi:
Substances chimiques
Bile Acids and Salts
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
189-196Références
Albillos A, de Gottardi A, Rescigno M. The gut-liver axis in liver disease: pathophysiological basis for therapy. J Hepatol 2020; 72:558–577.
Milosevic I, Vujovic A, Barac A, et al. Gut-liver axis, gut microbiota, and its modulation in the management of liver diseases: a review of the literature. Int J Mol Sci 2019; 20:395.
Brandl K, Kumar V, Eckmann L. Gut-liver axis at the frontier of host-microbial interactions. Am J Physiol Gastrointest Liver Physiol 2017; 312:G413–G419.
Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol 2017; 11:821–834.
Li T, Chiang JY. Bile acids as metabolic regulators. Curr Opin Gastroenterol 2015; 31:159–165.
Ahmad TR, Haeusler RA. Bile acids in glucose metabolism and insulin signalling- mechanisms and research needs. Nat Rev Endocrinol 2019; 15:701–712.
Theiler-Schwetz V, Zaufel A, Schlager H, et al. Bile acids and glucocorticoid metabolism in health and disease. Biochim Biophys Acta Mol Basis Dis 2019; 1865:243–251.
Kiriyama Y, Nochi H. The biosynthesis, signaling, and neurological functions of bile acids. Biomolecules 2019; 9:232.
Chiang JYL, Ferrell JM. Bile acid metabolism in liver pathobiology. Gene Expr 2018; 18:71–87.
Wang G, Huang S, Wang Y, et al. Bridging intestinal immunity and gut microbiota by metabolites. Cell Mol Life Sci 2019; 76:3917–3937.
Chen ML, Takeda K, Sundrud MS. Emerging roles of bile acids in mucosal immunity and inflammation. Mucosal Immunol 2019; 12:851–861.
Biagioli M, Carino A. Signaling from intestine to the host: how bile acids regulate intestinal and liver immunity. Handb Exp Pharmacol 2019; 256:95–108.
Sipka S, Bruckner G. The immunomodulatory role of bile acids. Int Arch Allergy Immunol 2014; 165:1–8.
Garcia M, Thirouard L, Sedès L, et al. Nuclear receptor metabolism of bile acids and xenobiotics: a coordinated detoxification system with impact on health and diseases. Int J Mol Sci 2018; 19:3630.
Shin DJ, Wang L. Bile acid-activated receptors: a review on FXR and other nuclear receptors. Handb Exp Pharmacol 2019; 256:51–72.
Kliewer SA, Mangelsdorf DJ. Bile acids as hormones: the FXR-FGF15/19 pathway. Dig Dis 2015; 33:327–331.
Matsubara T, Li F, Gonzalez FJ. FXR signaling in the enterohepatic system. Mol Cell Endocrinol 2013; 368:17–29.
Buchman CD, Chai SC, Chen T. A current structural perspective on PXR and CAR in drug metabolism. Expert Opin Drug Metab Toxicol 2018; 14:635–647.
Oladimeji PO, Chen T. PXR: more than just a master xenobiotic receptor. Mol Pharmacol 2018; 93:119–127.
Guo C, Chen WD, Wang YD. TGR5, not only a metabolic regulator. Front Physiol 2016; 26:646.
Keitel V, Häussinger D. Role of TGR5 (GPBAR1) in liver disease. Semin Liver Dis 2018; 38:333–339.
Kim H, Fang S. Crosstalk between FXR and TGR5 controls glucagon-like peptide 1 secretion to maintain glycemic homeostasis. Lab Anim Res 2018; 34:140–146.
Meadows V, Kennedy L, Kundu D, et al. Bile acid receptor therapeutics effects on chronic liver diseases. Front Med (Lausanne) 2020; 7:15.
Xiao L, Pan G. An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: the apical sodium-dependent bile acid transporter (SLC10A2/ASBT). Clin Res Hepatol Gastroenterol 2017; 41:509–515.
Ashby K, Navarro Almario EE, Tong W, et al. Review article: therapeutic bile acids and the risks for hepatotoxicity. Aliment Pharmacol Ther 2018; 47:1623–1638.
Schaap FG, Trauner M, Jansen PL. Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol 2014; 11:55–67.
Arab JP, Karpen SJ, Dawson PA, et al. Bile acids and nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives. Hepatology 2017; 65:350–362.
Trauner M, Fuchs CD, Halilbasic E, et al. New therapeutic concepts in bile acid transport and signaling for management of cholestasis. Hepatology 2017; 65:1393–1404.
Gadaleta RM, van Erpecum KJ, Oldenburg B, et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut 2011; 60:463–472.
Maxwell JR, Brown WA, Smith CL, et al. Methods of inducing inflammatory bowel disease in mice. Curr Protoc Pharmacol; Chapter 5: Unit 558 2009; doi: 10.1002/0471141755.ph0558s47.
doi: 10.1002/0471141755.ph0558s47
Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr 1991; 12:439–447.
Turner D, Otley AR, Mack D, et al. Development, validation, and evaluation of a paediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007; 133:423–432.
Daperno M, D’Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc 2004; 60:505–512.
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-amino- salicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987; 317:1625–1629.
Biagioli M, Carino A, Cipriani S, et al. The bile acid receptor GPBAR1 regulates the M1/M2 phenotype of intestinal macrophages and activation of GPBAR1 rescues mice from murine colitis. J Immunol 2017; 199:718–733.
Schneider KM, Albers S, Trautwein C. Role of bile acids in the gut liver axis. J Hepatol 2018; 68:1083–1085.
Islam Z, Horikawa A, Inui T, et al. Datasets of microarray analysis to identify Gpr137b-dependent interleukin-4-responsive genes in the mouse macrophage cell line RAW264. Data Brief 2019; 23:103669.
Perino A, Schoonjans K. TGR5 and immunometabolism: insights from physiology and pharmacology. Trends Pharmacol Sci 2015; 36:847–857.
Zhu JB, Xu S, Li J, et al. Farnesoid X receptor agonist obeticholic acid inhibits renal inflammation and oxidative stress during lipopolysaccharide-induced acute kidney injury. Eur J Pharmacol 2018; 5:60–68.
Vavassori P, Mencarelli A, Renga B, et al. The bile acid receptor FXR is a modulator of intestinal innate immunity. Immunol 2009; 15:6251–6261.
Kegami T, Honda A. Reciprocal interactions between bile acids and gut microbiota in human liver diseases. Hepatol Res 2018; 48:15–27.
Tripathi A, Debelius J, Brenner DA, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 2018; 15:785.
Shaler CR, Elhenawy W, Coombes BK. The unique lifestyle of Crohn's disease-associated adherent-invasive Escherichia coli. J Mol Biol 2019; 431:2970–2981.
Selyutina OY, Polyakov NE. Glycyrrhizic acid as a multifunctional drug carrier - from physicochemical properties to biomedical applications: a modern insight on the ancient drug. Int J Pharm 2019; 559:271–279.
Ming LJ, Yin AC. Therapeutic effects of glycyrrhizic acid. Nat Prod Commun 2013; 8:415–418.
Vitali R, Palone F, Cucchiara S, et al. Dipotassium glycyrrhizate inhibits HMGB1-dependent inflammation and ameliorates colitis in mice. PLoS One 2013; 8:e66527.