The FXR Agonist Obeticholic Acid Prevents Gut Barrier Dysfunction and Bacterial Translocation in Cholestatic Rats
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Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis. Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic and intestinal bile metabolism. We studied potential intestinal FXR dysfunction in a rat model of cholestatic liver injury and evaluated effects of obeticholic acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments were performed with Transwell supports. Vehicle-treated bile duct-ligated rats exhibited decreased FXR pathway expression in both jejunum and ileum, in association with increased gut permeability through increased claudin-2 expression and related to local and systemic recruitment of natural killer cells resulting in increased interferon-γ expression and BTL. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro, interferon-γ induced increased Escherichia coli translocation, which remained unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal barrier function by attenuating intestinal inflammation, leading to reduced BTL and thus demonstrating a crucial protective role for FXR in the gut-liver axis.
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FXR activation by GW4064 or obeticholic acid attenuates mucosal injury, ileal barrier permeability, bacterial overgrowth and bacterial translocation in mice and rats.
“Accordingly, FXR activation by agonists GW4064 or obeticholic acid (OCA) attenuates mucosal injury, ileal barrier permeability, bacterial overgrowth and bacterial translocation in mice and rats 20,21,141,142.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [141]
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Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190 · see citing works
Moreau, R., Jalan, R., Ginès, P., Pavesi, M., Angeli, P., Córdoba, J., Durand, F., Gustot, T., Saliba, F., Domenicali, M., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.042 · Cited by 3,041 · see citing works
Self-citationRole of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678 · see citing works
Mudaliar, S., Henry, R. R., Sanyal, A. J., Morrow, L., Marschall, H., Kipnes, M., Adorini, L., Sciacca, C. I., Clopton, P., Castelloe, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.042 · Cited by 931 · see citing works
Gadaleta, R. M., van Erpecum, K. J., Oldenburg, B., Willemsen, E. C. L., Renooij, W., Murzilli, S., Klomp, L. W. J., Siersema, P. D., Schipper, M. E. I., Danese, S., et al. (2011) · Gut · doi:10.1136/gut.2010.212159 · Cited by 870 · cited 2× · see citing works
“FXR deficiency has therefore been linked to increased intestinal permeability and BTL in noneliver-related gastrointestinal disorders, such as inflammatory bowel disease.(25,26) However, whether FXR dysfunction also relates to BTL in chronic liver disease (and also what are the underlying pathophysiological mechanisms…”
BackgroundResultTight Junction Pore and Leak Pathways: A Dynamic Duo
Shen, L., Weber, C. R., Raleigh, D. R., Yu, D., & Turner, J. R. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142150 · Cited by 867 · see citing works
Berg, R. D., & Garlington, A. W. (1979) · Infection and Immunity · doi:10.1128/iai.23.2.403-411.1979 · Cited by 845 · see citing works
Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers.
Madara, J. L., & Stafford, J. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113938 · Cited by 758 · see citing works
Pellicciari, R., Fiorucci, S., Camaioni, E., Clerici, C., Costantino, G., Maloney, P. R., Morelli, A., Parks, D. J., & Willson, T. M. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm025529g · Cited by 743 · see citing works
Wang, F., Graham, W. V., Wang, Y., Witkowski, E. D., Schwarz, B. T., & Turner, J. R. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62264-x · Cited by 692 · see citing works
Farnesoid X receptor antagonizes nuclear factor κB in hepatic inflammatory response
Wang, Y.-D., Chen, W.-D., Wang, M., Yu, D., Forman, B. M., & Huang, W. (2008) · Hepatology · doi:10.1002/hep.22519 · Cited by 639 · see citing works
Vanuytsel, T., van Wanrooy, S., Vanheel, H., Vanormelingen, C., Verschueren, S., Houben, E., Salim Rasoel, S., Tόth, J., Holvoet, L., Farré, R., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-305690 · Cited by 615 · see citing works
Self-citationBacterial translocation of enteric organisms in patients with cirrhosis
Cirera, I., Bauer, T., Navasa, M., Vilà, J., Grande, L., Taurá, P., Fuster, J., García‐Valdecasas, J. C., Lacy, A. M., Suárez, M. J., et al. (2001) · Journal of Hepatology · doi:10.1016/s0168-8278(00)00013-1 · Cited by 429 · see citing works
Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia
Vanheel, H., Vicario, M., Vanuytsel, T., Van Oudenhove, L., Martinez, C., Keita, Å. V., Pardon, N., Santos, J., Söderholm, J. D., Tack, J., et al. (2014) · Gut · doi:10.1136/gutjnl-2012-303857 · Cited by 424 · see citing works
Self-citationA Histologic Scoring System for Prognosis of Patients With Alcoholic Hepatitis
Altamirano, J., Miquel, R., Katoonizadeh, A., Abraldeṣ, J. G., Duarte‐Rojo, A., Louvet, A., Augustín, S., Mookerjee, R. P., Michelena, J., Smyrk, T. C., et al. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.01.018 · Cited by 421 · see citing works
Self-citationSpontaneous bacterial peritonitis: recent guidelines and beyond
Wiest, R., Krag, A. A., & Gerbes, A. (2011) · Gut · doi:10.1136/gutjnl-2011-300779 · Cited by 384 · see citing works
Bruewer, M., Utech, M., Ivanov, A. I., Hopkins, A. M., Parkos, C. A., & Nusrat, A. (2005) · The FASEB Journal · doi:10.1096/fj.04-3260com · Cited by 364 · see citing works
Reiberger, T., Ferlitsch, A., Payer, B. A., Mandorfer, M., Heinisch, B. B., Hayden, H., Lammert, F., Trauner, M. A., Peck‐Radosavljevic, M., & Vogelsang, H. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.12.011 · Cited by 328 · see citing works
Modica, S., Petruzzelli, M., Bellafante, E., Murzilli, S., Salvatore, L., Celli, N., Di Tullio, G., Palasciano, G., Moustafa, T., Halilbasic, E., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.10.028 · Cited by 275 · see citing works
Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis
Adorini, L., Pruzanski, M., & Shapiro, D. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.05.012 · Cited by 259 · see citing works
Navasa, M., Follo, A., Llovet, J., Clemente, G., Vargas, V, Rimola, A., Marco, F., Guarner, C., Forne, M., Planas, R., et al. (1996) · Gastroenterology · doi:10.1016/s0016-5085(96)70069-0 · Cited by 258 · see citing works
Verbeke, L., Farre, R., Trebicka, J., Komuta, M., Roskams, T., Klein, S., Elst, I. V., Windmolders, P., Vanuytsel, T., Nevens, F., et al. (2014) · Hepatology · doi:10.1002/hep.26939 · Cited by 258 · see citing works
Self-citationEarly features of acute-on-chronic alcoholic liver failure: a prospective cohort study
Katoonizadeh, A., Laleman, W., Verslype, C., Wilmer, A. P., Maleux, G. A., Roskams, T., & Nevens, F. (2010) · Gut · doi:10.1136/gut.2009.189639 · Cited by 252 · see citing works
Self-citationBacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites
García–Tsao, G., Lee, F., Barden, G. E., Cartun, R. W., & West, A. B. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90147-7 · Cited by 247 · see citing works
Bile acid-induced negative feedback regulation of the human ileal bile acid transporter
Neimark, E., Chen, F., Li, X., & Shneider, B. L. (2004) · Hepatology · doi:10.1002/hep.20295 · Cited by 234 · see citing works
McMahan, R. H., Wang, X. X., Cheng, L. L., Krisko, T., Smith, M., El Kasmi, K., Pruzanski, M., Adorini, L., Golden-Mason, L., Levi, M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.446575 · Cited by 225 · see citing works
Poupon, R. Y. (2012) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/s2210-7401(12)70015-3 · Cited by 224 · see citing works
Bellot, P., Garc´ıa-Paga´n, J. C., France´s, R., Abraldes, J. G., Navasa, M., Pe´rez-Mateo, M., Such, J., & Bosch, J. (2010) · Hepatology · doi:10.1002/hep.23918 · Cited by 219 · see citing works
Genome‐wide tissue‐specific farnesoid X receptor binding in mouse liver and intestine†
Thomas, A., Hart, S. N., Kong, B., Fang, J., Zhong, X., & Guo, G. L. (2009) · Hepatology · doi:10.1002/hep.23450 · Cited by 205 · see citing works
du Plessis, J., Vanheel, H., Janssen, C., Roos, L., Slavík, T., Stivaktas, P. I., Nieuwoudt, M., van Wyk, S. G., Vieira, W. A., Pretorius, E., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.01.038 · Cited by 178 · see citing works
Self-citationMencarelli, A., Renga, B., Migliorati, M., Cipriani, S., Distrutti, E., Santucci, L., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901347 · Cited by 177 · cited 1× · see citing works
“anti-inflammatory response with, in particular, a remarkable decrease in the number of NKCs, both locally in the MLNs and systemically in the spleen, consistent with findings by others on the hepatic level.(50) As a logical consequence, IFN-g levels (in parallel with the decreased number of NKCs in the INT-747etreated…”
ResultClark, E. C., Hoare, C. J., Tanianis-Hughes, J., Carlson, G., & Warhurst, G. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.01.046 · Cited by 171 · see citing works
Watson, C. J. E., Hoare, C. J., Garrod, D. R., Carlson, G., & Warhurst, G. (2005) · Journal of Cell Science · doi:10.1242/jcs.02630 · Cited by 171 · see citing works
Fickert, P., Fuchsbichler, A., Moustafa, T., Wagner, M., Zollner, G., Halilbasic, E., Stöger, U., Arrese, M., Pizarro, M., Solís, N., et al. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.090114 · Cited by 169 · see citing works
Bacterial Translocation in Acute and Chronic Portal Hypertension
Quigley, E. M. M., & García–Tsao, G. (1994) · Hepatology · doi:10.1002/hep.1840200145 · Cited by 164 · see citing works
Ariza, X., Castellote, J., Lora-Tamayo, J., Girbau, A., Salord, S., Rota, R., Ariza, J., & Xiol, X. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.11.010 · Cited by 154 · see citing works
Bacterial translocation in acute and chronic portal hypertension
García–Tsao, G., Albillos, A., Barden, G. E., & West, B. A. (1993) · Hepatology · doi:10.1002/hep.1840170622 · Cited by 141 · see citing works
Intestinal permeability is increased in patients with advanced cirrhosis.
Pascual, S., Such, J. M., Esteban, A., Zapater, P., Casellas, J. A., Aparicio, J. R., Girona, E., Gutiérrez, A., Carnices, F., Palazón, J. M., et al. (2003) · PubMed · Cited by 137 · see citing works
Llovet, J. M., Bartolí, R., Planas, R., Cabré, E., Jiménez, M., Urban, A., Ojanguren, I., Arnal, J., & Gassull, M. À. (1994) · Gut · doi:10.1136/gut.35.11.1648 · Cited by 135 · see citing works
FXR-mediated regulation of eNOS expression in vascular endothelial cells
Jiang, L., Wilson, A. S., Kuruba, R., Zhang, Q., Gao, X., He, F., Zhang, L., Pitt, B. R., Xie, W., & Song, L. (2007) · Cardiovascular Research · doi:10.1093/cvr/cvm016 · Cited by 123 · see citing works
Umgelter, A., Reindl, W., Miedaner, M., Schmid, R. M., & Huber, W. (2009) · Infection · doi:10.1007/s15010-008-8060-9 · Cited by 121 · see citing works
Laleman, W., Verbeke, L., Meersseman, P., Wauters, J., van Pelt, J. F., Cassiman, D. M., Wilmer, A. P., Verslype, C., & Nevens, F. (2011) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.11.47 · Cited by 98 · see citing works
Self-citationWallon, C., Braaf, Y., Wolving, M., Olaison, G., & Söderholm, J. D. (2005) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520510012235 · Cited by 97 · see citing works
Vanwijngaerden, Y.-M., Wauters, J., Langouche, L., Perre, S. V., Liddle, C., Coulter, S., Vanderborght, S., Roskams, T., Wilmer, A. P., den Berghe, G. V., et al. (2011) · Hepatology · doi:10.1002/hep.24582 · Cited by 96 · see citing works
Self-citationZuckerman, M. J., Menzies, I. S., Ho, H., Gregory, G. G., Casner, N. A., Crane, R., & Hernandez, J. A. (2004) · Digestive Diseases and Sciences · doi:10.1023/b:ddas.0000026307.56909.21 · Cited by 79 · see citing works
A stable model of cirrhotic portal hypertension in the rat: thioacetamide revisited
Laleman, W., Elst, I. V., Zeegers, M., Servaes, R., Libbrecht, L. J., Roskams, T., Fevery, J., & Nevens, F. (2006) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2006.01620.x · Cited by 77 · see citing works
Self-citationObstructive jaundice promotes bacterial translocation in humans.
Ma, K., It, K., Çöl, C., Tekelı, A., Tanık, A., & Köksoy, C. (1999) · PubMed · Cited by 67 · see citing works
Verbeke, L., Nevens, F., & Laleman, W. (2011) · Critical Care · doi:10.1186/cc10424 · Cited by 51 · see citing works
Self-citationChatterjee, S., Bijsmans, I. T. G. W., van Mil, S. W. C., Augustijns, P., & Annaert, P. (2013) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.10.020 · Cited by 44 · see citing works
Self-citationThalheimer, U., Iorio, F. D., Capra, F., Lleò, M. D. M., Zuliani, V., Ghidini, V., Tafi, M. C., Caburlotto, G., Gennari, M., Burroughs, A. K., et al. (2010) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e32833b4b03 · Cited by 43 · see citing works
Smyth, D. R., McKay, C. M., Gulbransen, B. D., Phan, V., Wang, A., & McKay, D. M. (2012) · Cellular Microbiology · doi:10.1111/j.1462-5822.2012.01796.x · Cited by 29 · see citing works
Vanwijngaerden, Y.-M., Langouche, L., Derde, S., Liddle, C., Coulter, S., den Berghe, G. V., & Mesotten, D. (2013) · Shock · doi:10.1097/shk.0000000000000046 · Cited by 16 · see citing works
Intestinal permeability assessed by 51Cr-EDTA in rats with CCl4 - induced cirrhosis
Ramos, A. R. L., Matte, Ú. D. S., Goldani, H. A. S., de Oliveira, O. L. M., Vieira, S. M. G., & da Silveira, T. R. (2010) · Arquivos de Gastroenterologia · doi:10.1590/s0004-28032010000200014 · Cited by 9 · see citing works
Ubeda, M., Borrero, M. J., Lario, M., Muñoz, L., Conde, E. D. V., Rodríguez, M., Lledó, L., García-Bermejo, L., Álvarez-Mon, M., & Albillos, A. (2014) · Journal of Hepatology · doi:10.1016/s0168-8278(14)60155-0 · Cited by 5 · see citing works
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Fukui, H., & Wiest, R. (2016) · Inflammatory Intestinal Diseases · doi:10.1159/000444436 · Cited by 6,820 · see citing works
The gut-liver axis in liver disease: Pathophysiological basis for therapy
Albillos, A., de Gottardi, A., & Rescigno, M. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.10.003 · Cited by 2,166 · see citing works
Gut-liver axis: Pathophysiological concepts and clinical implications
Tilg, H., Adolph, T. E., & Trauner, M. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.017 · Cited by 843 · see citing works
Mouries, J., Brescia, P., Silvestri, A., Spadoni, I., Sorribas, M., Wiest, R., Mileti, E., Galbiati, M., Invernizzi, P., Adorini, L., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.08.005 · Cited by 688 · see citing works
The gut microbiome and liver cancer: mechanisms and clinical translation
Yu, L.-X., & Schwabe, R. F. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.72 · Cited by 634 · see citing works
Fleishman, J. S., & Kumar, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01811-6 · Cited by 577 · see citing works
Intestinal Barrier in Human Health and Disease
Tommaso, N. D., Gasbarrini, A., & Ponziani, F. R. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182312836 · Cited by 552 · see citing works
Molecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481 · see citing works
Pierantonelli, I., & Svegliati‐Baroni, G. (2018) · Transplantation · doi:10.1097/tp.0000000000002480 · Cited by 459 · see citing works
Acute-on-chronic liver failure in cirrhosis
Arroyo, V., Moreau, R., Kamath, P. S., Jalan, R., Ginès, P., Nevens, F., Fernández, J., To, U. K., García–Tsao, G., & Schnabl, B. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.41 · Cited by 442 · see citing works
Self-citationTargeting the gut-liver axis in liver disease
Wiest, R., Albillos, A., Trauner, M., Bajaj, J. S., & Jalan, R. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.05.007 · Cited by 423 · see citing works
Bile acids as modulators of gut microbiota composition and function
Larabi, A. B., Masson, H. L. P., & Bäumler, A. J. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2172671 · Cited by 420 · see citing works
Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex
Rizzetto, L., Fava, F., Tuohy, K. M., & Selmi, C. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.05.008 · Cited by 331 · see citing works
The microbiota in cirrhosis and its role in hepatic decompensation
Trebicka, J., Macnaughtan, J., Schnabl, B., Shawcross, D. L., & Bajaj, J. S. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2020.11.013 · Cited by 276 · see citing works
Self-citationGuts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease
Hegyi, P., Maléth, J., Walters, J. R., Hofmann, A. F., & Keely, S. J. (2018) · Physiological Reviews · doi:10.1152/physrev.00054.2017 · Cited by 269 · see citing works
Microbiota, cirrhosis, and the emerging oral-gut-liver axis
Acharya, C., Sahingur, S. E., & Bajaj, J. S. (2017) · JCI Insight · doi:10.1172/jci.insight.94416 · Cited by 256 · see citing works
Sorribas, M., Jakob, M. O., Yılmaz, B., Li, H., Stutz, D., Noser, Y., Gottardi, A. D., Moghadamrad, S., Hassan, M., Albillos, A., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.06.017 · Cited by 256 · see citing works
Verbeke, L., Mannaerts, I., Schierwagen, R., Govaere, O., Klein, S., Vander Elst, I., Windmolders, P., Farre, R., Wenes, M., Mazzone, M., et al. (2016) · Scientific Reports · doi:10.1038/srep33453 · Cited by 236 · see citing works
Self-citationBile acid metabolism and signalling in liver disease
Fuchs, C. D., Simbrunner, B., Baumgartner, M., Campbell, C., Reiberger, T., & Trauner, M. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.09.032 · Cited by 246 · see citing works
Gut–liver axis, cirrhosis and portal hypertension: the chicken and the egg
Arab, J. P., Martín‐Mateos, R., & Shah, V. H. (2017) · Hepatology International · doi:10.1007/s12072-017-9798-x · Cited by 229 · see citing works
Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
Iwakiri, Y., & Trebicka, J. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100316 · Cited by 237 · see citing works
Self-citationAntibiotic prophylaxis in cirrhosis: Good and bad
Fernández, J., Tandon, P., Mensa, J., & García–Tsao, G. (2015) · Hepatology · doi:10.1002/hep.28330 · Cited by 205 · see citing works
Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives
Hu, H., Lin, A., Kong, M., Yao, X., Yin, M., Xia, H., Ma, J., & Liu, H. (2019) · Journal of Gastroenterology · doi:10.1007/s00535-019-01649-8 · Cited by 208 · see citing works
Foley, M. H., O’Flaherty, S., Allen, G., Rivera, A. J., Stewart, A. K., Barrangou, R., & Theriot, C. M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017709118 · Cited by 205 · see citing works
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Trebicka, J., Bork, P., Krag, A. A., & Arumugam, M. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00376-3 · Cited by 203 · see citing works
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Inoue, T., Nakayama, J., Moriya, K., Kawaratani, H., Momoda, R., Ito, K., Iio, E., Nojiri, S., Fujiwara, K., Yoneda, M., et al. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/ciy205 · Cited by 183 · see citing works
Úbeda, M., Lario, M., Muñoz, L., Borrero, M.-J., Rodríguez-Serrano, M., Sánchez-Díaz, A.-M., del Campo, R., Lledó, L., Pastor, Ó., García-Bermejo, L., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.12.010 · Cited by 178 · see citing works
Schwabl, P., Hambruch, E., Seeland, B. A., Hayden, H., Wagner, M., Garnys, L., Strobel, B., Schubert, T.-L., Riedl, F., Mitteregger, D., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.12.005 · Cited by 178 · see citing works
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Li, H. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i27.8304 · Cited by 167 · see citing works
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Friedman, E. S., Li, Y., Shen, T.-C. D., Jiang, J., Chau, L., Adorini, L., Babakhani, F., Edwards, J., Shapiro, D., Zhao, C., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.022 · Cited by 149 · see citing works
Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease
Suk, K. T., & Kim, D. J. (2019) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2019.1569513 · Cited by 133 · see citing works
Breakthroughs in therapies for NASH and remaining challenges
Ratziu, V., Francque, S., & Sanyal, A. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.04.002 · Cited by 132 · see citing works
Bile acid receptors and gastrointestinal functions
Ticho, A. L., Malhotra, P., Dudeja, P. K., Gill, R. K., & Alrefai, W. A. (2019) · Liver Research · doi:10.1016/j.livres.2019.01.001 · Cited by 131 · see citing works
Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation
Xiong, X., Ren, Y., Cui, Y., Li, R., Wang, C., & Zhang, Y. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.11.083 · Cited by 125 · see citing works
Gut microbiome in primary sclerosing cholangitis: A review
Little, R., Wine, E., Kamath, B. M., Griffiths, A. M., & Ricciuto, A. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i21.2768 · Cited by 125 · see citing works
Bile acids and their receptors in regulation of gut health and diseases
Lin, S., Wang, S., Wang, P., Tang, C., Wang, Z., Chen, L., Luo, G., Chen, H., Liu, Y., Feng, B., et al. (2022) · Progress in Lipid Research · doi:10.1016/j.plipres.2022.101210 · Cited by 123 · see citing works
Role of bile acids in inflammatory liver diseases
Evangelakos, I., Heeren, J., Verkade, E., & Kuipers, F. (2021) · Seminars in Immunopathology · doi:10.1007/s00281-021-00869-6 · Cited by 121 · see citing works
Leaky Gut and Gut-Liver Axis in Liver Cirrhosis: Clinical Studies Update
Fukui, H. (2020) · Gut and Liver · doi:10.5009/gnl20032 · Cited by 115 · see citing works
Gut-liver axis signaling in portal hypertension
Simbrunner, B., Mandorfer, M., Trauner, M., & Reiberger, T. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i39.5897 · Cited by 113 · see citing works
Review article: therapeutic aspects of bile acid signalling in the gut‐liver axis
Simbrunner, B., Trauner, M. A., & Reiberger, T. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16602 · Cited by 107 · see citing works
Gut microbiome and liver disease
Betrapally, N. S., Gillevet, P. M., & Bajaj, J. S. (2016) · Translational research · doi:10.1016/j.trsl.2016.07.005 · Cited by 104 · see citing works
The multifactorial mechanisms of bacterial infection in decompensated cirrhosis
der Merwe, V., Chokshi, S., Bernsmeier, C., & Albillos, A. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2020.11.029 · Cited by 102 · see citing works
Bile Acid Alterations Are Associated With Insulin Resistance, but Not With NASH, in Obese Subjects
Legry, V., Francque, S., Haas, J. T., Verrijken, A., Caron, S., Chávez‐Talavera, O., Vallez, E., Vonghia, L., Dirinck, E. L., Verhaegen, A., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01397 · Cited by 102 · see citing works
Critical roles of bile acids in regulating intestinal mucosal immune responses
Sun, R., Xu, C., Feng, B., Gao, X., & Liu, Z. (2021) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848211018098 · Cited by 99 · see citing works
Piano, S. S., Bunchorntavakul, C., Marciano, S., & Reddy, K. R. (2024) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(24)00078-5 · Cited by 95 · see citing works
The functions of gut microbiota-mediated bile acid metabolism in intestinal immunity
He, Y., Shaoyong, W., Chen, Y., Li, M., Gan, Y., Sun, L., Liu, Y., Wang, Y., & Jin, M. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.05.015 · Cited by 95 · see citing works
The Role of Gut Microbiota in Some Liver Diseases: From an Immunological Perspective
Wang, L., Cao, Z.-M., Zhang, L., Li, J.-M., & Lv, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.923599 · Cited by 87 · see citing works
Systemic Inflammation and Acute-on-Chronic Liver Failure: Too Much, Not Enough
Laleman, W., Clària, J., der Merwe, S. V., Moreau, R., & Trebicka, J. (2018) · Canadian Journal of Gastroenterology and Hepatology · doi:10.1155/2018/1027152 · Cited by 74 · see citing works
Self-citationRadun, R., & Trauner, M. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1731707 · Cited by 81 · see citing works
Anderson, K. M., & Gayer, C. P. (2021) · Cells · doi:10.3390/cells10113206 · Cited by 82 · see citing works
Novel perspectives in the management of decompensated cirrhosis
Bernardi, M., & Caraceni, P. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0045-2 · Cited by 79 · see citing works
TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation
Labiano, I., Agirre-Lizaso, A., Olaizola, P., Echebarria, A., Huici-Izagirre, M., Olaizola, I., Esparza-Baquer, A., Sharif, O., Hijona, E., Milkiewicz, P., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.05.044 · Cited by 78 · see citing works
Obeticholic acid protects against carbon tetrachloride‐induced acute liver injury and inflammation
Zhang, D.-G., Zhang, C., Wang, J.-X., Wang, B.-W., Wang, H., Zhang, Z.-H., Chen, Y.-H., Lu, Y., Tao, L., Wang, J.-Q., et al. (2017) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2016.11.006 · Cited by 75 · see citing works
Meadows, V., Kennedy, L., Ekser, B., Kyritsi, K., Kundu, D., Zhou, T.-H., Chen, L.-X., Pham, L., Wu, N., Demieville, J., et al. (2021) · Hepatology · doi:10.1002/hep.32028 · Cited by 55 · see citing works
Bile acids and cardiovascular function in cirrhosis
Voiosu, A. M., Wiese, S. S., Voiosu, T. A., Bendtsen, F., & Møller, S. (2017) · Liver International · doi:10.1111/liv.13394 · Cited by 66 · see citing works
Gustot, T., Stadlbauer, V., Laleman, W., Alessandria, C., & Thursz, M. R. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2020.12.005 · Cited by 71 · see citing works
Self-citationGut Microbiota and Host Reaction in Liver Diseases
Fukui, H. (2015) · Microorganisms · doi:10.3390/microorganisms3040759 · Cited by 64 · see citing works
Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats
Ceulemans, L. J., Verbeke, L., Decuypere, J.-P., Farré, R., Hertogh, G. D., Lenaerts, K., Jochmans, I., Monbaliu, D. R. L., Nevens, F., Tack, J. F., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169331 · Cited by 62 · see citing works
Self-citationYang, F., Tang, X., Ding, L., Zhou, Y., Yang, Q., Gong, J., Wang, G., Wang, Z., & Yang, L. (2016) · Scientific Reports · doi:10.1038/srep33052 · Cited by 61 · see citing works
Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease
Baffy, G. (2018) · Digestive Diseases and Sciences · doi:10.1007/s10620-017-4903-5 · Cited by 61 · see citing works
Blood‐Bile Barrier: Morphology, Regulation, and Pathophysiology
Pradhan-Sundd, T., & Monga, S. P. (2019) · Gene Expression · doi:10.3727/105221619x15469715711907 · Cited by 54 · see citing works
Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction
Sauerbruch, T., Hennenberg, M., Trebicka, J., & Beuers, U. H. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.718783 · Cited by 51 · see citing works
Self-citationBacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
Simbrunner, B., Caparrós, E., Neuwirth, T., Schwabl, P., Königshofer, P., Bauer, D. J. M., Marculescu, R., Trauner, M. A., Scheiner, B., Stary, G., et al. (2023) · Hepatology International · doi:10.1007/s12072-023-10496-y · Cited by 51 · see citing works
Gut-liver axis: Pathophysiological concepts and medical perspective in chronic liver diseases
Rodrigues, S. G., der Merwe, V., Krag, A. A., & Wiest, R. (2024) · Seminars in Immunology · doi:10.1016/j.smim.2023.101859 · Cited by 51 · see citing works
Nevens, F., Trauner, M. A., & Manns, M. P. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.10.007 · Cited by 51 · see citing works
Self-citationThe gut microbiota-bile acid axis in cholestatic liver disease
Sun, D.-Y., Xie, C., Zhao, Y., Liao, J.-M., Li, S.-S., Zhang, Y.-N., Wang, D.-D., Hua, K., Gu, Y.-C., Du, J.-B., et al. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00830-x · Cited by 53 · see citing works
Intestinal permeability in a patient with liver cirrhosis
Aguirre-Valádez, J., Rivera-Espinosa, L., Méndez-Guerrero, O., Chávez-Pacheco, J. L., Juárez, I. G., & Torre, A. (2016) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s115902 · Cited by 50 · see citing works
Pharmacologic prevention of variceal bleeding and rebleeding
Baiges, A., Hernández–Gea, V., & Bosch, J. (2017) · Hepatology International · doi:10.1007/s12072-017-9833-y · Cited by 49 · see citing works
Farnesoid-X receptor as a therapeutic target for inflammatory bowel disease and colorectal cancer
Zhou, M.-J., Wang, D., Li, X., Cao, Y., Yi, C.-X., Ocansey, D. K. W., Zhou, Y., & Mao, F. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1016836 · Cited by 51 · see citing works
Advances in intestinal epithelium and gut microbiota interaction
Yang, S., Liu, H., & Liu, Y. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1499202 · Cited by 48 · see citing works
Simbrunner, B., Villesen, I. F., Königshofer, P., Scheiner, B., Bauer, D. J. M., Paternostro, R., Schwabl, P., Timelthaler, G., Ramazanova, D., Wöran, K., et al. (2022) · Liver International · doi:10.1111/liv.15365 · Cited by 47 · see citing works
Chen, J., Zheng, M., Liu, J., Luo, Y., Yang, W., Yang, J., Liu, J., Jingxing, Z., Xu, C., Zhao, F., et al. (2019) · Obesity · doi:10.1002/oby.22627 · Cited by 47 · see citing works
Hullar, M. A. J., Jenkins, I., Randolph, T. W., Curtis, K. R., Monroe, K. R., Ernst, T. M., Shepherd, J., Stram, D. O., Cheng, I. C., Kristal, B. S., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1965463 · Cited by 45 · see citing works
Hernandez, G. V., Smith, V. A., Melnyk, M., Burd, M. A., Sprayberry, K. A., Edwards, M. S., Peterson, D. G., Bennet, D. C., Fanter, R. K., Columbus, D. A., et al. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00344.2019 · Cited by 44 · see citing works
Li, W., Chen, H., & Tang, J. (2024) · Pathogens · doi:10.3390/pathogens13080702 · Cited by 45 · see citing works
Oxidation of fish oil exacerbates alcoholic liver disease by enhancing intestinal dysbiosis in mice
Feng, R., Ma, L., Wang, M., Liu, C., Yang, R., Su, H., Yang, Y., & Wan, J. (2020) · Communications Biology · doi:10.1038/s42003-020-01213-8 · Cited by 44 · see citing works
Plasma Exchange in Acute and Acute on Chronic Liver Failure
Maiwall, R., & Sarin, S. (2021) · Seminars in liver disease (Print) · doi:10.1055/s-0041-1730971 · Cited by 38 · see citing works
Chen, Y., Hu, X., Zhou, Y., Yu, Z., Fu, L., Zhang, G.-B., Bo, Q., Wang, H., Zhang, C., & Xu, D. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1601331 · Cited by 43 · see citing works
Xiao, Y., Wang, Y., Liu, Y., Wang, W., Tian, X., Chen, S., Lu, Y., Du, J., & Cai, W. (2021) · Liver International · doi:10.1111/liv.14906 · Cited by 43 · see citing works
Review of the Relationships Between Human Gut Microbiome, Diet, and Obesity
Patloka, O., Komprda, T., & Franke, G. (2024) · Nutrients · doi:10.3390/nu16233996 · Cited by 45 · see citing works
Guo, H., Hassan, H. M., Zhang, Y., Dong, S.-Z., Ding, P., Wang, T., Sun, L., Zhang, L., & Jiang, Z. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw098 · Cited by 41 · see citing works
Intrahepatic cholestasis induced by α-naphthylisothiocyanate can cause gut-liver axis disorders
Chen, Z., Wu, Y., Wang, B., Fang, J., Gan, C., Sang, C., Dun, Z., Luosang, T., Wang, Q., Zeren, D., et al. (2021) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2021.103672 · Cited by 40 · see citing works
Modulation of gut microbiome in nonalcoholic fatty liver disease: pro-, pre-, syn-, and antibiotics
Cho, M. S., Kim, S. Y., Suk, K. T., & Kim, B. (2018) · The Journal of Microbiology · doi:10.1007/s12275-018-8346-2 · Cited by 40 · see citing works
Current and Future Treatments in the Fight against Non-Alcoholic Fatty Liver Disease
Smeuninx, B., Boslem, E., & Febbraio, M. A. (2020) · Cancers · doi:10.3390/cancers12071714 · Cited by 39 · see citing works
Tang, Y., Fan, Y., Wang, Y., Wang, D., Huang, Q., Chen, T., Cao, X., Wen, C., Shen, X., Li, J., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116658 · Cited by 38 · see citing works
Gu, Y., Song, Y., Yin, H., Lin, S., Zhang, X., Che, L., Lin, Y., Xu, S., Feng, B., Wu, D., et al. (2017) · Journal of Animal Science · doi:10.2527/jas.2016.0911 · Cited by 37 · see citing works
Bile Formation and the Enterohepatic Circulation
Dawson, P. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809954-4.00041-4 · Cited by 36 · see citing works
Controversies in the Mechanism of Total Parenteral Nutrition Induced Pathology
Kumar, J., & Teckman, J. H. (2015) · Children · doi:10.3390/children2030358 · Cited by 33 · see citing works
Tang, K., Kong, D., Peng, Y., Guo, J., Zhong, Y., Yu, H., Mai, Z., Chen, Y., Chen, Y., Cui, T., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1000444 · Cited by 33 · see citing works
Novel treatment options for portal hypertension
Schwabl, P., & Laleman, W. (2017) · Gastroenterology report · doi:10.1093/gastro/gox011 · Cited by 31 · see citing works
Self-citationMetabolic-Associated Fatty Liver Disease and the Gut Microbiota
Barber, T. M., Hanson, P., & Weickert, M. O. (2023) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2023.01.004 · Cited by 31 · see citing works
Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR‐S1PR2 ‐dependent mechanism
Xu, W., Lu, C., Zhang, F., Shao, J., & Zheng, S. (2016) · IUBMB Life · doi:10.1002/iub.1492 · Cited by 31 · see citing works
Guo, Z., He, K., Pang, K., Yang, D., Lyu, C., Xu, H., & Wu, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084321 · Cited by 29 · see citing works
Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease
van Zutphen, T., Bertolini, A., de Vries, H. D., Bloks, V. W., de Boer, J. F., Jonker, J. W., & Kuipers, F. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_233 · Cited by 30 · see citing works
Gut–Liver Axis Dysregulation in Portal Hypertension: Emerging Frontiers
Lombardi, M., Troisi, J., Motta, B. M., Torre, P., Masarone, M., & Persico, M. (2024) · Nutrients · doi:10.3390/nu16071025 · Cited by 27 · see citing works
Intestine-specific FXR agonists as potential therapeutic agents for colorectal cancer
Yin, Y., Wang, M., Gu, W., & Chen, L. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114430 · Cited by 27 · see citing works
Liu, H., Kohmoto, O., Sakaguchi, A., Hori, S., Tochigi, M., Tada, K., Lee, Y., Kikuchi, K., & Ishizuka, S. (2022) · Food and Chemical Toxicology · doi:10.1016/j.fct.2022.113136 · Cited by 27 · see citing works
Advances in the pharmacological management of bacterial peritonitis
Pörner, D., von Vietinghoff, S., Nattermann, J., Strassburg, C. P., & Lutz, P. L. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1915288 · Cited by 26 · see citing works
Novel prevention strategies for bacterial infections in cirrhosis
Yan, K. G., & García–Tsao, G. (2016) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2016.1145663 · Cited by 26 · see citing works
- Authors
- Verbeke, L., Farre, R., Verbinnen, B., Covens, K., Vanuytsel, T., Verhaegen, J., Komuta, M., Roskams, T., Chatterjee, S., Annaert, P., Elst, I. V., Windmolders, P., Trebicka, J., Nevens, F., & Laleman, W.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Thomas More Kempen (BE)
- KU Leuven (BE)
- University of Bonn (DE)
- Corresponding author
- Verbeke, Len
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 185
- Issue
- 2
- Pages
- 409-419
- ISSN
- 0002-9440 (ISSN-L)
- OpenAlex
- W2104582722
- Cited by
- 225
- References
- 54
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 24 · 2023: 11 · 2022: 21 · 2021: 28 · 2020: 18 · 2019: 22 · 2018: 13 · 2017: 18 · 2016: 16 · 2015: 8
- FWCI
- 8.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- Scientific Research–Flanders
- Deutsche Forschungsgemeinschaft (SFB TRR57 project 18)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- obeticholic acid, FXR agonists, bacterial translocation, intestinal barrier dysfunction, cholestasis, bile duct ligation, intestinal permeability, claudin-2, claudin-1, occludin, tight junction proteins, natural killer cells, interferon-gamma, intestinal inflammation, gut-liver axis, liver cirrhosis, Escherichia coli
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Chenodeoxycholic Acid, Cholestasis, Escherichia coli, Gene Expression Regulation, Ileum, Male, Cytokines, Rats, Wistar, Receptors, Cytoplasmic and Nuclear, Bacterial Translocation, Rats
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