Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats - PubMed (original) (raw)
. 2016 May;64(5):1049-1057.
doi: 10.1016/j.jhep.2015.12.010. Epub 2015 Dec 23.
Margaret Lario 1, Leticia Muñoz 1, María-José Borrero 1, Macarena Rodríguez-Serrano 2, Ana-María Sánchez-Díaz 3, Rosa Del Campo 3, Lourdes Lledó 4, Óscar Pastor 5, Laura García-Bermejo 2, David Díaz 6, Melchor Álvarez-Mon 6, Agustín Albillos 7
Affiliations
- PMID: 26723896
- DOI: 10.1016/j.jhep.2015.12.010
Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats
María Úbeda et al. J Hepatol. 2016 May.
Abstract
Background & aims: In advanced cirrhosis, gut bacterial translocation is the consequence of intestinal barrier disruption and leads to bacterial infection. Bile acid abnormalities in cirrhosis could play a role in the integrity of the intestinal barrier and the control of microbiota, mainly through the farnesoid X receptor. We investigated the long-term effects of the farnesoid X receptor agonist, obeticholic acid, on gut bacterial translocation, intestinal microbiota composition, barrier integrity and inflammation in rats with CCl4-induced cirrhosis with ascites.
Methods: Cirrhotic rats received a 2-week course of obeticholic acid or vehicle starting once ascites developed. We then determined: bacterial translocation by mesenteric lymph node culture, ileum expression of antimicrobial peptides and tight junction proteins by qPCR, fecal albumin loss, enteric bacterial load and microbiota composition by qPCR and pyrosequencing of ileum mucosa-attached contents, and intestinal inflammation by cytometry of the inflammatory infiltrate.
Results: Obeticholic acid reduced bacterial translocation from 78.3% to 33.3% (p<0.01) and upregulated the expression of the farnesoid X receptor-associated gene small heterodimer partner. Treatment improved ileum expression of antimicrobial peptides, angiogenin-1 and alpha-5-defensin, tight junction proteins zonulin-1 and occludin, and reduced fecal albumin loss and liver fibrosis. Enteric bacterial load normalized, and the distinctive mucosal microbiota of cirrhosis was reduced. Gut immune cell infiltration was reduced and inflammatory cytokine and Toll-like receptor 4 expression normalized.
Conclusions: In ascitic cirrhotic rats, obeticholic acid reduces gut bacterial translocation via several complementary mechanisms at the intestinal level. This agent could be used as an alternative to antibiotics to prevent bacterial infection in cirrhosis.
Keywords: Ascites; Dysbiosis; Inflammation; Permeability.
Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Comment in
- Evolving insights in the pathophysiology of complications of cirrhosis: The farnesoid X receptor (FXR) to the rescue?
Laleman W, Trebicka J, Verbeke L. Laleman W, et al. Hepatology. 2016 Nov;64(5):1792-1794. doi: 10.1002/hep.28771. Epub 2016 Sep 30. Hepatology. 2016. PMID: 27531824 No abstract available.
Similar articles
- Effect of artesunate supplementation on bacterial translocation and dysbiosis of gut microbiota in rats with liver cirrhosis.
Chen YX, Lai LN, Zhang HY, Bi YH, Meng L, Li XJ, Tian XX, Wang LM, Fan YM, Zhao ZF, Han DW, Ji C. Chen YX, et al. World J Gastroenterol. 2016 Mar 14;22(10):2949-59. doi: 10.3748/wjg.v22.i10.2949. World J Gastroenterol. 2016. PMID: 26973391 Free PMC article. - The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats.
Verbeke L, Farre R, Verbinnen B, Covens K, Vanuytsel T, Verhaegen J, Komuta M, Roskams T, Chatterjee S, Annaert P, Vander Elst I, Windmolders P, Trebicka J, Nevens F, Laleman W. Verbeke L, et al. Am J Pathol. 2015 Feb;185(2):409-19. doi: 10.1016/j.ajpath.2014.10.009. Epub 2015 Jan 12. Am J Pathol. 2015. PMID: 25592258 - Long-term cannabinoid type 2 receptor agonist therapy decreases bacterial translocation in rats with cirrhosis and ascites.
Yang YY, Hsieh SL, Lee PC, Yeh YC, Lee KC, Hsieh YC, Wang YW, Lee TY, Huang YH, Chan CC, Lin HC. Yang YY, et al. J Hepatol. 2014 Nov;61(5):1004-13. doi: 10.1016/j.jhep.2014.05.049. Epub 2014 Jun 19. J Hepatol. 2014. PMID: 24953022 - Microbiota and the gut-liver axis: bacterial translocation, inflammation and infection in cirrhosis.
Giannelli V, Di Gregorio V, Iebba V, Giusto M, Schippa S, Merli M, Thalheimer U. Giannelli V, et al. World J Gastroenterol. 2014 Dec 7;20(45):16795-810. doi: 10.3748/wjg.v20.i45.16795. World J Gastroenterol. 2014. PMID: 25492994 Free PMC article. Review. - The use of obeticholic acid for the management of non-viral liver disease: current clinical practice and future perspectives.
Gitto S, Guarneri V, Sartini A, Andreone P. Gitto S, et al. Expert Rev Gastroenterol Hepatol. 2018 Feb;12(2):165-171. doi: 10.1080/17474124.2018.1399060. Epub 2017 Nov 3. Expert Rev Gastroenterol Hepatol. 2018. PMID: 29082798 Review.
Cited by
- The gut-liver axis in hepatobiliary diseases.
Ichikawa M, Okada H, Nakamoto N, Taniki N, Chu PS, Kanai T. Ichikawa M, et al. Inflamm Regen. 2024 Jan 8;44(1):2. doi: 10.1186/s41232-023-00315-0. Inflamm Regen. 2024. PMID: 38191517 Free PMC article. Review. - Altenusin, a fungal metabolite, alleviates TGF-β1-induced EMT in renal proximal tubular cells and renal fibrosis in unilateral ureteral obstruction.
Thipboonchoo N, Fongsupa S, Sureram S, Sa-Nguansak S, Kesornpun C, Kittakoop P, Soodvilai S. Thipboonchoo N, et al. Heliyon. 2024 Jan 19;10(3):e24983. doi: 10.1016/j.heliyon.2024.e24983. eCollection 2024 Feb 15. Heliyon. 2024. PMID: 38318047 Free PMC article. - The Hepatic Sinusoid in Aging and Disease: Update and Advances From the 20th Liver Sinusoid Meeting.
Ortega-Ribera M, Hunt NJ, Gracia-Sancho J, Cogger VC. Ortega-Ribera M, et al. Hepatol Commun. 2020 Apr 27;4(7):1087-1098. doi: 10.1002/hep4.1517. eCollection 2020 Jul. Hepatol Commun. 2020. PMID: 32626839 Free PMC article. - Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr-/-.Leiden Mice.
Morrison MC, Verschuren L, Salic K, Verheij J, Menke A, Wielinga PY, Iruarrizaga-Lejarreta M, Gole L, Yu WM, Turner S, Caspers MPM, Martínez-Arranz I, Pieterman E, Stoop R, van Koppen A, van den Hoek AM, Mato JM, Hanemaaijer R, Alonso C, Kleemann R. Morrison MC, et al. Hepatol Commun. 2018 Oct 29;2(12):1513-1532. doi: 10.1002/hep4.1270. eCollection 2018 Dec. Hepatol Commun. 2018. PMID: 30556039 Free PMC article. - Antimicrobial proteins: intestinal guards to protect against liver disease.
Hendrikx T, Schnabl B. Hendrikx T, et al. J Gastroenterol. 2019 Mar;54(3):209-217. doi: 10.1007/s00535-018-1521-8. Epub 2018 Nov 3. J Gastroenterol. 2019. PMID: 30392013 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources