The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease
Abstract
BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is characterised by chronic intestinal inflammation, resulting from dysregulation of the mucosal immune system and compromised intestinal epithelial barrier function. The bile salt, nuclear farnesoid X receptor (FXR), was recently implicated in intestinal antibacterial defence and barrier function. The aim of this study was to investigate the therapeutic potential of FXR agonists in the treatment of intestinal inflammation in complementary in vivo and in vitro models. METHODS: Colitis was induced in wild-type (WT) and Fxr-null mice using dextran sodium sulfate, and in WT mice using trinitrobenzenesulfonic acid. Mice were treated with vehicle or the FXR agonist INT-747, and colitis symptoms were assessed daily. Epithelial permeability assays and cytokine expression analysis were conducted in mouse colon and enterocyte-like cells (Caco-2/HT29) treated with medium or INT-747. Inflammatory cytokine secretion was determined by ELISA in various human immune cell types. RESULTS: INT-747-treated WT mice are protected from DSS- and TNBS-induced colitis, as shown by significant reduction of body weight loss, epithelial permeability, rectal bleeding, colonic shortening, ulceration, inflammatory cell infiltration and goblet cell loss. Furthermore, Fxr activation in intestines of WT mice and differentiated enterocyte-like cells downregulates expression of key proinflammatory cytokines and preserves epithelial barrier function. INT-747 significantly decreases tumour necrosis factor α secretion in activated human peripheral blood mononuclear cells, purified CD14 monocytes and dendritic cells, as well as in lamina propria mononuclear cells from patients with IBD. CONCLUSIONS: FXR activation prevents chemically induced intestinal inflammation, with improvement of colitis symptoms, inhibition of epithelial permeability, and reduced goblet cell loss. Furthermore, FXR activation inhibits proinflammatory cytokine production in vivo in the mouse colonic mucosa, and ex vivo in different immune cell populations. The findings provide a rationale to explore FXR agonists as a novel therapeutic strategy for IBD.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“FXR agonists are known to alleviate endoplasmic reticulum stress and suppress oxidative damage by upregulating antioxidant and anti-apoptotic pathways [42, 43].”
From High-throughput human microfluidic organoid-on-a-chip platform for modeling liver diseases and screening nanotherapeutics. (2026) · cites this paper as [42]
In the citing paper
“Multiple reports regarding TGR5 function (Gadaleta et al., 2011;Hartmann et al., 2018;Inagaki et al., 2006;Vavassori et al., 2009) have indicated that a very fine balance between host-and microbiota-produced bile acids is required to support epithelial barrier function and control the inflammatory response in the intestine.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gadaleta et al., 2011
In the citing paper
“Activation of FXR inhibits intestinal inflammation and protects the intestinal barrier in IBD (Gadaleta et al., 2011).”
From Bacteroides dorei BDX-01 alleviates DSS-induced experimental colitis in mice by regulating intestinal bile salt hydrolase activity and the FXR-NLRP3 signaling pathway (2023) · cites this paper as Gadaleta et al., 2011
In the citing paper
“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 [21]
In the citing paper
“treatment with a synthetic agonist of BAR has protective effects in mouse models of colitis, whereas BAR-deficient (Nr1h4−/−) mice exhibit exacerbated pathology (Gadaleta et al., 2011; Vavassori et al., 2009).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Gadaleta et al., 2011
In the citing paper
“In the small intestine, they are also very important for the maintenance of epithelial barrier function (Gadaleta et al., 2011; Inagaki et al., 2006).”
From Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism (2017) · cites this paper as Gadaleta et al., 2011
Citations
Cites
Podolsky, D. K. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020831 · Cited by 3,183
Hidalgo, I. J., Raub, T. J., & Borchardt, R. T. (1989) · Gastroenterology · doi:10.1016/s0016-5085(89)80072-1 · Cited by 2,396
Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis
Sartor, R. B. (2006) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep0528 · Cited by 1,806
Targeting bile‐acid signalling for metabolic diseases
Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2619 · Cited by 1,422 · cited 1×
“Currently, phase 1 and 2 studies with INT-747 are being performed in patients with metabolic and chronic liver diseases, indicating the safe applicability of this class of compounds for the treatment of human disease.(42) Figure 8 INT-747 inhibits IFNg, IL-17 and TNFa production by lymphocyte-enriched LPMCs from IBD p…”
BackgroundPenna, G., & Adorini, L. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.5.2405 · Cited by 1,257
Self-citationRegulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
Inagaki, T., Moschetta, A., Lee, Y.-K., Peng, L., Zhao, G., Downes, M., Yu, R. T., Shelton, J. M., Richardson, J. A., Repa, J. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509592103 · Cited by 1,164 · cited 2×
“Fxr-null mice exhibited compromised intestinal integrity at baseline, with further deterioration after bile duct ligation, which was not prevented by FXR agonist treatment.(15) Recently, FXR activation was also shown to protect against hepatic inflammation presumably by repression of NF-kB signalling in mice.”
BackgroundSelf-citationAngiogenins: a new class of microbicidal proteins involved in innate immunity
Hooper, L. V., Stappenbeck, T. S., Hong, C. V., & Gordon, J. I. (2003) · Nature Immunology · doi:10.1038/ni888 · Cited by 947
Ananthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D. J., & Suchy, F. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011610200 · Cited by 804
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
Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function
Cario, E., Gerken, G., & Podolsky, D. K. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.02.056 · Cited by 697
Cited by
Sorted by citations
Items 401–500 of 875
Protective Effect and Mechanism of Placenta Extract on Liver
Shen, L., Fan, L., Zhang, Y., Zhu, Y., Zong, X., Peng, G., & Cao, S. (2022) · Nutrients · doi:10.3390/nu14235071 · Cited by 37
The role of goblet cells in Crohn’ s disease
Wang, Z., & Shen, J. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01220-w · Cited by 35
“Gadaleta and colleagues focused on the effects of Fxr agonists [144].”
BackgroundQiao, Y., Tang, X., Liu, Z., Ocansey, D. K. W., Zhou, M., Shang, A., & Mao, F. (2024) · Pharmaceuticals · doi:10.3390/ph17050607 · Cited by 32
Guo, Q., Chen, L., Liu, Z., & Zheng, B. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c01595 · Cited by 31
Samat, H. N. A., Razali, N. N., Mahadzir, H., Muhammad, T. S. T., Ling, K., Mansor, N. I., & Abidin, S. Z. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26188905 · Cited by 34
“Gut microbiota dysbiosis-induced alterations in bile acid metabolism impair FXR signalling, leading to increased intestinal permeability and inflammation [140].”
Bacterial translocation in critical illness
Krentz, T., & Allen, S. J. (2017) · Journal of Small Animal Practice · doi:10.1111/jsap.12626 · Cited by 31
Interactions between noroviruses, the host, and the microbiota
Walker, F. C., & Baldridge, M. T. (2019) · Current Opinion in Virology · doi:10.1016/j.coviro.2019.04.001 · Cited by 31
How Changes in the Nutritional Landscape Shape Gut Immunometabolism
Tan, J., Ni, D., Ribeiro, R. V., Pinget, G. V., & Macia, L. (2021) · Nutrients · doi:10.3390/nu13030823 · Cited by 29
“Activation of FXR also has anti-inflammatory effects, associated with decreased macrophage activation and preserved epithelial integrity in mouse models of colitis [230].”
BackgroundLuan, Z., Ming, W., Sun, X., Zhang, C., Zhou, Y., Zheng, F., Yang, Y., Guan, Y., & Zhang, X. (2021) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00193.2021 · Cited by 31
Metabolic-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
Porez, G., Gross, B. S., Prawitt, J., Gheeraert, C., Berrabah, W., Alexandre, J., Staels, B., & Lefèbvre, P. (2013) · Endocrinology · doi:10.1210/en.2013-1263 · Cited by 34
Pleiotropic roles of FXR in liver and colorectal cancers
Huang, X., Fan, M., & Huang, W. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111543 · Cited by 32
Hollow CeO2 with ROS-Scavenging Activity to Alleviate Colitis in Mice
Yang, J., Zhou, J., Zhao, Y., Zhu, L., Luo, G., & Ge, B. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s317261 · Cited by 30
Ioannou, P., Katsoulieris, E. N., & Afratis, N. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083621 · Cited by 34
“These SBAs interact with nuclear and membrane receptors TGR5, FXR, and PXR, influencing inflammation, gut barrier function, and MMP expression [207,208].”
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 31
Epithelial sensing of microbiota-derived signals
Eshleman, E. M., & Alenghat, T. (2021) · Genes and Immunity · doi:10.1038/s41435-021-00124-w · Cited by 30
“Moreover, direct FXR stimulation induced anti-inflammatory effects and protected mice against models of colitis [105, 106], demonstrating the importance of bile acid signaling on regulating intestinal homeostasis.”
BackgroundCao, L., Qin, R., & Liu, J.-B. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110080 · Cited by 26
Bijsmans, I. T. G. W., Guercini, C., Pittol, J. M. R., Omta, W. A., Milona, A., Lelieveld, D., Egan, D., Pellicciari, R., Gioiello, A., & van Mil, S. V. (2015) · Scientific Reports · doi:10.1038/srep14086 · Cited by 32
Self-citationLuo, Z., Zhou, W., Xie, T., Xu, W., Shi, C., Xiao, Z., Si, Y., Ma, Y., Ren, Q., Di, L., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.04.027 · Cited by 31
Pastore, M., Lori, G., Gentilini, A., Taddei, M. L., Maira, G. D., Campani, C., Recalcati, S., Invernizzi, P., Marra, F., & Raggi, C. (2020) · Cells · doi:10.3390/cells9030596 · Cited by 28
Zhang, K., Yao, Y., Wang, M., Liu, F., Wang, Q., Ma, H., Xie, Y., Ma, Y., Dai, P., Zhu, C., et al. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153683 · Cited by 29
Lu, Z., Feng, L., Jiang, W., Wu, P., Liu, Y., Jiang, J., Kuang, S., Tang, L., Li, S., Zhong, C.-B., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1010221 · Cited by 28
“When pathogens penetrate the mechanical barrier of the intestinal wall (including mucus layer, epithelium, and Apical junction complex), a secondary line of defense is initiated (immune cell dominance), triggering an immune response (45).”
BackgroundNuclear Receptors in the Pathogenesis and Management of Inflammatory Bowel Disease
Ning, L., Lou, X., Zhang, F., & Xu, G. (2019) · Mediators of Inflammation · doi:10.1155/2019/2624941 · Cited by 27
“FXR activation in the intestines of wild-type mice and in enterocytes downregulates the expression of the proinflammatory cytokines IL-6, MCP-1, and IL-1β and preserves epithelial barrier integrity [90].”
BackgroundBile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease
Chen, W., Wang, D., Deng, X., Zhang, H., Dong, D., Su, T., Lu, Q., Jiang, C., Ni, Q., Cui, Y., et al. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2323231 · Cited by 29
“36,37 The secondary BAs LCA and DCA are the most important ligands of FXR and TGR5.”
BackgroundLiu, C., Cai, T., Cheng, Y., Bai, J., Li, M., Gu, B., Huang, M., & Fu, W. (2024) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202300927 · Cited by 27
Li, S., Han, B., Li, J., Lv, Z., Jiang, H., Liu, Y., Yang, X., Lu, J., & Zhang, Z. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c02349 · Cited by 28
Huang, L., Yin, P., Liu, F., Liu, Y., Liu, Y., & Xia, Z. (2019) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.13246 · Cited by 27
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
Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis
Lian, F., WANG, Y., Xiao, Y., Wu, X., Xu, H., Liang, L., & Yang, X. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4159 · Cited by 27
“Previous studies have associated FXR with inflammatory and immune‑mediated diseases (25,26).”
FXR Deletion in Hepatocytes does not Affect the Severity of Alcoholic Liver Disease in Mice
Zhang, M., Kong, B., Huang, M.-X., Wan, R.-X., Armstrong, L. E., Schumacher, J. D., Rizzolo, D., Chow, M. D., Lee, Y.-H., & Guo, G. L. (2018) · Digestive and Liver Disease · doi:10.1016/j.dld.2018.04.009 · Cited by 26
Rzeczycki, P., Pęciak, O., Plust, M., & Droździk, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262411897 · Cited by 30
“Thus, via maintaining anti-inflammatory tone, FXR-active bile acids from the microbiota might indirectly preserve higher P-gp/BCRP levels [81,82].”
van de Wiel, S. M. W., de Waart, D. R., Elferink, R. P. J. O., & van de Graaf, S. F. J. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.11.011 · Cited by 26
“FXR activation dampens intestinal inflammation, improves epithelial barrier function and permeability, and inhibits proinflammatory cytokine production in the mouse colonic mucosa.(28,29) Notably, clofazimine also is incidentally used in inflammatory bowel disease and has an anti-inflammatory capacity.”
BackgroundGut Microbiota, Peroxisome Proliferator-Activated Receptors, and Hepatocellular Carcinoma
Yu, Q., Wu, L., Ji, J., Feng, J., Dai, W., Li, J., Wu, J., & Guo, C. (2020) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s277870 · Cited by 27
Xiao, Q., Yu, F., Yan, L., Zhao, H., & Zhang, F. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1026070 · Cited by 28
van Schaik, F. D. M., Gadaleta, R. M., Schaap, F. G., van Mil, S. W. C., Siersema, P. D., Oldenburg, B., & van Erpecum, K. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049706 · Cited by 25
“In two murine models for colitis, we recently showed that the administration of a semi-synthetic FXR agonist ameliorates intestinal inflammation, with improvement of colitis symptoms, preservation of intestinal barrier function, reduced goblet cell loss and inhibition of proinflammatory cytokine expression [11].”
BackgroundSelf-citationZhao, J., Duan, L., Li, J., Yao, C., Wang, G., Mi, J., Yu, Y., Ding, L., Zhao, Y., Yan, G., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116807 · Cited by 26
Ning, S., Zhang, Z., Zhou, C., Wang, B., Liu, Z., & Feng, B. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1457218 · Cited by 29
The Gut‒Liver Axis in Liver Disease: Molecular Mechanisms and Therapeutic Targets
Chen, Z., Liao, S., Wu, S., Chen, S., Tang, Q., Zhou, L., Li, X., Hu, H., Xu, J., Zhang, A., et al. (2025) · MedComm · doi:10.1002/mco2.70458 · Cited by 29
Jain, A. K., Sharma, A., Arora, S., Blomenkamp, K., Jun, I. C., Luong, R., Westrich, D. J., Mittal, A., Buchanan, P. M., Guzmán, M. A., et al. (2016) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607116661838 · Cited by 26
Yan, M., Hou, L., Cai, Y., Wang, H., Ma, Y., Geng, Q., Jiang, W., & Tang, W. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.906452 · Cited by 25
“Activation of the FXR pathway or the FXR agonists protects the mucosal integrity by regulating the expression of downstream genes related to mucosa protection and defense against inflammation in rodents (Vavassori et al., 2009; Gadaleta et al., 2011).”
BackgroundKoutsounas, I. S., Theocharis, S. E., Delladetsima, I. K., Patsouris, E., & Giaginis, C. (2015) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.999664 · Cited by 25
“The role of FXR as a modulator of intestinal inflammation and as an important player in enteroprotection is emphasized by the findings that FXR genetic variants are associated with IBD, together with observations on FXR expression being altered in CD and on FXR promoting intestinal barrier integrity and antibacterial…”
BackgroundBile Acids and Biliary Fibrosis
Aseem, S. O., Hylemon, P. B., & Zhou, H. (2023) · Cells · doi:10.3390/cells12050792 · Cited by 28
“FXR has immune-modulating effects through interactions with NF-κB in hepatocytes and various immune cells, leading to the suppression of NF-κBinduced inflammatory cytokines [7,63,64].”
BackgroundBile salt signaling and bile salt-based therapies in cardiometabolic disease
Groenen, C., Nguyen, T.-A., Paulusma, C. C., & van de Graaf, S. F. J. (2024) · Clinical Science · doi:10.1042/cs20230934 · Cited by 25
Targeted metabolomics reveals aberrant profiles of serum bile acids in patients with schizophrenia
Qing, Y., Wang, P., Cui, G., Zhang, J., Liang, K., Xia, Z., Wang, P., He, L., & Jia, W. P. (2022) · Schizophrenia · doi:10.1038/s41537-022-00273-5 · Cited by 25
Xiao, F., Gao, X., Hu, H., Le, J., Chen, Y., Shu, X., Liang, Z., Xu, Y., Wang, Y., & Zhang, T. (2022) · Nutrients · doi:10.3390/nu14214463 · Cited by 25
Lv, Y., Lou, Y., Liu, A., Cheng, Q., Yang, G., Xu, C., Luo, Y., Lou, J., Yu, J., Fang, Y., et al. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.11.018 · Cited by 26
Dehondt, H., Marino, A., Butruille, L., Mogilenko, D. A., Loubota, A. C. N., Chávez‐Talavera, O., Dorchies, E., Vallez, E., Haas, J. T., Derudas, B., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101686 · Cited by 25
Zweers, S. J. L. B., de Vries, E. M., Leníček, M., Tolenaars, D., de Waart, D. R., Koelfat, K. V. K., Groen, A. K., Damink, S. W. M. O., Beuers, U. H., Ponsioen, C. Y., et al. (2016) · Hepatology International · doi:10.1007/s12072-016-9769-7 · Cited by 24
Ipharraguerre, I. R., Pastor, J. J., Gavaldà‐Navarro, A., Villarroya, F., & Mereu, A. (2018) · Scientific Reports · doi:10.1038/s41598-018-32107-9 · Cited by 26
Update on the Epidemiology and Management of Microscopic Colitis
Peery, A. F., Khalili, H., Münch, A., & Pardi, D. S. (2024) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.08.026 · Cited by 23
Liu, X., Kang, W., Li, J., Li, X., Yang, P., Shi, M., Wang, Z., Wang, Y., Medina, A. I. V., Liu, D., et al. (2024) · Journal of Pineal Research · doi:10.1111/jpi.70005 · Cited by 24
Ablation of liver Fxr results in an increased colonic mucus barrier in mice
Ijssennagger, N., van Rooijen, K. S., Magnúsdóttir, S., Pittol, J. M. R., Willemsen, E. C. L., de Zoete, M. R., Baars, M. J. D., Stege, P. B., Colliva, C., Pellicciari, R., et al. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100344 · Cited by 23
Self-citationYang, J.-Z., Zhang, K.-K., He, J.-T., Chen, L., Ding, J., Liu, J.-L., Li, J.-H., Liu, Y., Li, X., Zhao, D., et al. (2023) · Toxicology · doi:10.1016/j.tox.2023.153447 · Cited by 23
Gut Dysbiosis and Blood-Brain Barrier Alteration in Hepatic Encephalopathy: From Gut to Brain
Shahbazi, A., Sepehrinezhad, A., Vahdani, E., Jamali, R., Ghasempour, M., Massoudian, S., Negah, S. S., & Larsen, F. S. (2023) · Biomedicines · doi:10.3390/biomedicines11051272 · Cited by 25
The cell biology of the intestinal epithelium and its relation to inflammatory bowel disease
Deuring, J. J., de Haar, C. G., Kuipers, E. J., Peppelenbosch, M. P., & van der Woude, C. J. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.12.020 · Cited by 23
Goyal, N. P., Rana, A., Bijjem, K. R. V., & Kumar, P. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2014.12.018 · Cited by 23
Nolan, J., Johnston, I. M., & Walters, J. R. F. (2012) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.12.66 · Cited by 23
Farnesoid X receptor as a regulator of fuel consumption and mitochondrial function
Han, C. Y., Kim, T. H., Koo, J. H., & Kim, S. G. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0812-y · Cited by 23
Negroni, A., Fiaschini, N., Palone, F., Vitali, R., Colantoni, E., Laudadio, I., Oliva, S., Aloi, M., Cucchiara, S., & Stronati, L. (2020) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000002759 · Cited by 24
Alvaro, D., Carpino, G., Craxì, A., Floreani, A., Moschetta, A., & Invernizzi, P. (2020) · Liver International · doi:10.1111/liv.14627 · Cited by 23
Self-citationGil‐Gómez, A., Brescia, P., Rescigno, M., & Romero‐Gómez, M. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1723752 · Cited by 24
Oleanolic Acid Improves Gut Atrophy Induced by Parenteral Nutrition
Jain, A. K., Wen, J. X., Blomenkamp, K., Arora, S., Blaufuss, T. A., Rodrigues, J., Long, J. P., Neuschwander‐Tetri, B. A., & Teckman, J. H. (2015) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607115583536 · Cited by 23
Sun, H., Su, X., Liu, Y., Li, G., & Du, Q. (2023) · iScience · doi:10.1016/j.isci.2023.108392 · Cited by 22
Microbiota substances modulate dendritic cells activity: A critical view
Shvets, Y. V., Khranovska, N., Senchylo, N., Ostapchenko, D., Tymoshenko, I., Onysenko, S., Kobyliak, N. M., & Falalyeyeva, T. M. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27125 · Cited by 26
Intestinal flora and bile acid interactions impact the progression of diabetic kidney disease
Xu, J., Wang, N., Yang, L., Zhong, J., & Chen, M. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1441415 · Cited by 23
Wang, X., Zhang, B., & Jiang, R. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1467197 · Cited by 22
Disentangling the nutrition-microbiota liaison in inflammatory bowel disease
Florio, M., Crudele, L., Sallustio, F., Moschetta, A., Cariello, M., & Gadaleta, R. M. (2025) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2025.101349 · Cited by 22
Self-citationPratt, M., Forbes, J. D., Knox, N., Bernstein, C. N., & Domselaar, G. V. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.716604 · Cited by 23
Wu, Y., Mo, R., Zhang, M., Zhou, W., & Li, D. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.786682 · Cited by 22
“FXR deficiency aggravates chemically induced intestinal inflammation, whereas small molecule FXR agonist treatment relieves this with repression of proinflammatory cytokine expression, reduction of epithelial permeability, and preservation epithelial barrier function (11).”
BackgroundDas, B. K. (2022) · Apmis · doi:10.1111/apm.13282 · Cited by 25
“They have a direct antimicrobial influence and an indirect action via farnesoid X receptor (FXR)-induced antimicrobial peptides that regulate the proliferation and attachment of gut microbes [68].”
BackgroundDeciphering the role of gut metabolites in non-alcoholic fatty liver disease
Ralli, T., Saifi, Z., Tyagi, N., Vidyadhari, A., Aeri, V., & Kohli, K. (2022) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2022.2142091 · Cited by 22
“Additionally, they also cause release of antimicrobial peptides like angio-genin 1 (Vavassori et al. 2009; Gadaleta et al. 2011; Schwenger et al. 2019).”
BackgroundEmerging roles of host and microbial bioactive lipids in inflammatory bowel diseases
Kayama, H., & Takeda, K. (2023) · European Journal of Immunology · doi:10.1002/eji.202249866 · Cited by 21
Wang, B., Han, D. W., Hu, X., Chen, J., Liu, Y., & Wu, J. (2024) · Microbiological Research · doi:10.1016/j.micres.2024.127865 · Cited by 24
Ni, Q., Cai, C., Ren, S., Zhang, J., Zhao, Y., Wei, X., Ge, Y., Wang, C., Li, W., Wu, P., et al. (2021) · Aquaculture Research · doi:10.1111/are.15140 · Cited by 21
Kumar, A., Al-Hassi, H. O., Steed, H., Phipps, O., & Brookes, M. (2022) · Canadian Journal of Gastroenterology and Hepatology · doi:10.1155/2022/8416578 · Cited by 21
“FXR also controls several genes that protect against intestinal inflammation, intestinal permeability, and bacterial overgrowth [1, 24].”
BackgroundAn update on the effects of food-derived active peptides on the intestinal microecology
Mu, J., Lin, Q., & Liang, Y. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2094889 · Cited by 21
“Helicobacter pylori inhibits tryptophan metabolism and affects immune regulation, as tryptophan concentration is negatively correlated with the occurrence and development of diseases (Fu, Guan, and Wang 2018; Gadaleta et al. 2011; Hisamatsu et al. 2012; Romani et al. 2008).”
BackgroundYang, J.-Y., Liu, M., Lv, L. L., Guo, J.-R., He, K.-Y., Zhang, H., Wang, K., Cui, C.-Y., Yan, B., Du, D., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.932294 · Cited by 21
“The expression and function of FXR in the intestine (especially the ileum), immune cells, and endothelial tissues have recently been characterized (Gadaleta et al., 2011; Verbeke et al., 2014).”
BackgroundHill, D. R., & Buck, R. H. (2023) · Nutrients · doi:10.3390/nu15102339 · Cited by 23
Li, S., Xu, K., Cheng, Y., Chen, L., Yi, A., Xiao, Z., Zhao, X., Chen, M., Tian, Y., Wei, M., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1188455 · Cited by 24
Cheng, Q., Inaba, Y., Lu, P., Xu, M., He, J., Zhao, Y., Guo, G. L., Kuruba, R., de la Vega, R., Evans, R. G., et al. (2015) · Molecular Endocrinology · doi:10.1210/me.2014-1337 · Cited by 22
Mao, J., Chen, X., Wang, C., Li, W., & Li, J. (2020) · Oncology Letters · doi:10.3892/ol.2020.11545 · Cited by 21
“…which FXR suppresses tumor growth remains unclear, but it may involve protecting the colonic epithelium from inflammation and ameliorating BA toxicity by upregulating intracellular BA binding proteins and efflux transporters and downregulating influx transporters and de novo BA synthesis (10-12).”
BackgroundIntestinal failure to produce FGF19: A culprit in intestinal failure–associated liver disease?
van Erpecum, K. J., & Schaap, F. G. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.03.012 · Cited by 22
“For some time, gut microbiota have been appreciated as key determinants of intestinal inflammation and impaired intestinal barrier function, and FXR has recently been implicated in the prevention of intestinal bacterial overgrowth, maintenance of intestinal barrier integrity [7] and pathogenesis of Crohn’s disease [8–…”
BackgroundFXR acts as a therapeutic target for ulcerative colitis via suppressing ferroptosis
Zhao, C., Li, X., Mu, M., Quan, L., Yuan, H., Zheng, J., Zhao, W., Sun, X., & Yu, J. (2025) · Molecular Medicine · doi:10.1186/s10020-025-01305-3 · Cited by 20
“FXR activation not only prevented goblet cell loss and decreased epithelial permeability but also inhibited proinflammatory cytokine secretion in various primary human immune cell types and alleviated NF-kB-medi-ated immune responses in enterocytes (Gadaleta et al. 2011).”
Aldriwesh, M. G., Alotibi, R. S., Alqurainy, N., Alrabiah, S., Arafah, A. M., Alghoribi, M. F., & Ajina, R. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2607076 · Cited by 21
Zhu, Y., Xu, S., Lu, Y., Wei, Y., Yao, B., Guo, F., Zheng, X., Wang, Y., He, Y., Jin, L.-H., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00590 · Cited by 17
Isidori, M., Corbee, R. J., & Trabalza‐Marinucci, M. (2022) · Veterinary Sciences · doi:10.3390/vetsci9020037 · Cited by 24
“In a murine study, TGR-5 activation by related bile acid ligands suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated inflammatory response following lipopolysaccharide injection in wild-type mice but not in TGR-5 knockout mice [85].”
BackgroundGillard, J., Picalausa, C., Ullmer, C., Adorini, L., Staels, B., Tailleux, A., & Leclercq, I. A. (2022) · Nutrients · doi:10.3390/nu14132707 · Cited by 20
Self-citationLi, Y., Wang, K., Ding, J., Sun, S., Ni, Z., & Yu, C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.954684 · Cited by 21
The emerging microbiome‐based approaches to IBD therapy: From SCFAs to urolithin A
Rudiansyah, M., Jasim, S. A., Azizov, B., Samusenkov, V. O., Abdelbasset, W. K., Yasin, G., Mohammad, H. J., Jawad, M. A., Mahmudiono, T., Hosseini‐Fard, S. R., et al. (2022) · Journal of Digestive Diseases · doi:10.1111/1751-2980.13131 · Cited by 20
“Activation of BA receptors prevents against experimental colitis, and may also have an anti-inflammatory impact.(161) Mice lacking FXRs have reduced intestinal barrier and decreased antimicrobial protection in the small intestine.”
BackgroundRole of the Gut–Liver Axis in the Pathobiology of Cholangiopathies: Basic and Clinical Evidence
Bragazzi, M. C., Venere, R., Vignone, A., Alvaro, D., & Cardinale, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076660 · Cited by 21
“In addition, FXR activation via OCA represses chemically-induced intestinal inflammation in mice, suggesting the possible role of FXR in inflammatory bowel disease [52].”
BackgroundInfluentialKim, Y., Kim, H.-Y., Jang, J.-T., & Hong, S. (2023) · Molecules · doi:10.3390/molecules28248099 · Cited by 20
“It is composed of enterocytes that are tightly connected through intercellular junctions [8].”
BackgroundLiu, Y., Xiao, Y., Chen, S., Tian, X., Wang, W., Wang, Y., & Cai, W. (2021) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003135 · Cited by 20
“Enterocyte-like cells differentiated by FXR activation decrease proinflammatory cytokine levels, which might ameliorate intestinal inflammation (16).”
BackgroundMarzano, M., Fosso, B., Colliva, C., Notario, E., Passeri, D., Intranuovo, M., Gioiello, A., Adorini, L., Pesole, G., Pellicciari, R., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113380 · Cited by 21
Self-citationQian, S., Su, Z., Lin, J., Hou, Q., Wang, X., Li, Y., Wang, J., Huang, C., Wang, Z., Cubero, F. J., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02224-w · Cited by 24
“FXR is a crucial factor in regulating immunity within the gastrointestinal tract and exerts an anti-inflammatory role in DSS-induced colitis [15].”
Bile acid‐activated receptors in innate and adaptive immunity: targeted drugs and biological agents
Cheung, K. C. P., Ma, J., Loiola, R. A., Chen, X., & Jia, W. P. (2023) · European Journal of Immunology · doi:10.1002/eji.202250299 · Cited by 22
Effects of bile acid metabolism on intestinal health of livestock and poultry
Jia, H., & Dong, N. (2024) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.13969 · Cited by 19
Roles of Bile Acid-Activated Receptors in Monocytes-Macrophages and Dendritic Cells
Jia, H., He, X., Jiang, T., & Kong, F. (2025) · Cells · doi:10.3390/cells14120920 · Cited by 21
“Gadaleta et al. (2011) demonstrated that activation of FXR by the selective agonist INT-747 can reduce the severity of DSS and TNBS-induced colitis in mice, leading to decreased production of the pro-inflammatory cytokine TNF-α in DCs [50].”
Primary Sclerosing Cholangitis: New Approaches to Diagnosis, Surveillance and Treatment
Trauner, M., Halilbasic, E., Baghdasaryan, A., Moustafa, T., Krones, E., Fickert, P., Hofer, H., & Penner, E. (2012) · Digestive Diseases · doi:10.1159/000341123 · Cited by 20
Therapeutic Role of Bile Acids and Nuclear Receptor Agonists in Fibrosing Cholangiopathies
Trauner, M., Halilbasic, E., Kazemi-Shirazi, L., Kienbacher, C., Staufer, K., Traussnigg, S., & Hofer, H. (2014) · Digestive Diseases · doi:10.1159/000360517 · Cited by 19
Wasinger, V. C., Lu, K., Yau, Y. Y., Nash, J., Lee, J., Chang, J., Paramsothy, S., Kaakoush, N. O., Mitchell, H. M., & Leong, R. W. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-69746-w · Cited by 20
Metadata
- Authors
- 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., Penna, G., Laverny, G., Adorini, L., Moschetta, A., & Mil, S. W. C. V.
- Affiliations
- University Medical Center Utrecht (NL)
- Mario Negri Sud Foundation (IT)
- Corresponding author
- Mil, Saskia W C van
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2011-01-17
- Volume
- 60
- Issue
- 4
- Pages
- 463-472
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2134059673
- Cited by
- 870
- References
- 43
- Citations by year
- 2026: 72 · 2025: 87 · 2024: 95 · 2023: 75 · 2022: 96 · 2021: 84 · 2020: 59 · 2019: 46 · 2018: 35 · 2017: 44 · 2016: 40 · 2015: 36 · 2014: 29 · 2013: 35 · 2012: 21
- FWCI
- 19.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- Intercept Pharmaceuticals
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- farnesoid X receptor, FXR agonists, inflammatory bowel disease, colitis, intestinal barrier function, epithelial permeability, goblet cell loss, inflammatory cytokines, TNF-α, dendritic cells, monocytes, lamina propria, bile salts, DSS-induced colitis
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Chenodeoxycholic Acid, Colon, Disease Models, Animal, Drug Evaluation, Preclinical, Gene Expression Regulation, Humans, Ileum, Intestinal Absorption, Mice, Inbred C57BL, Trinitrobenzenesulfonic Acid, Tumor Necrosis Factor-alpha, Inflammatory Bowel Diseases, Cytokines, Dextran Sulfate, Receptors, Cytoplasmic and Nuclear, Inflammation Mediators, Caco-2 Cells, Reverse Transcriptase Polymerase Chain Reaction, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
