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
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 875
The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases
Fogelson, K. A., Dorrestein, P. C., Zarrinpar, A., & Knight, R. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.022 · Cited by 177
Liu, S., Kang, W., Mao, X., Ge, L., Du, H., Li, J., Hou, L., Liu, D., Yin, Y., Liu, Y., et al. (2022) · Journal of Pineal Research · doi:10.1111/jpi.12812 · Cited by 167
“Specifically, emerging evidence have indicated that FXR participated in regulating the epithelial barrier function by regulating mucosal immune response and gut antibacterial growth, and prevented the bacterial translocation.(50,51) Thus, we guess that the beneficial effects of MT on the intestine and liver may be rel…”
BackgroundCiaula, A. D., Baj, J., Garruti, G., Celano, G., Angelis, M. D., Wang, H. H., Palo, D. M. D., Bonfrate, L., Wang, D. Q. ‐., & Portincasa, P. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082648 · Cited by 166
Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity
Su, L., Gao, Y., & Yang, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1127743 · Cited by 174
“A reduced number of activated DCs in the colon of mice administered with INT-747/obetiCA was also observed.”
BackgroundInfluentialRinella, M. E., Dufour, J.-F., Anstee, Q. M., Goodman, Z., Younossi, Z., Harrison, S. A., Loomba, R., Sanyal, A. J., Bonacci, M., Trylesinski, A., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.10.029 · Cited by 164
FXR in liver physiology: Multiple faces to regulate liver metabolism
Panzitt, K., & Wagner, M. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166133 · Cited by 170
Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease
Sultan, S., El‐Mowafy, M., Elgaml, A., Ahmed, T. A., Hassan, H., & Mottawea, W. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.715506 · Cited by 170
The gut vascular barrier: a new player in the gut–liver–brain axis
Brescia, P., & Rescigno, M. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.06.007 · Cited by 163
Recipient factors in faecal microbiota transplantation: one stool does not fit all
Danne, C., Rolhion, N., & Sokol, H. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00441-5 · Cited by 154
Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease
Banfi, D., Moro, E., Bosi, A., Bistoletti, M., Cerantola, S., Crema, F., Maggi, F., Giron, M. C., Giaroni, C., & Baj, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041623 · Cited by 160
“To date, FMT is an established treatment for C. difficile infection and is also being considered for other gastrointestinal diseases such as IBD, IBS, hepatic steatosis, and hepatic encephalopathy [357].”
BackgroundMethodInfluentialSaponins as modulators of nuclear receptors
Zhang, T., Zhong, S., Li, T., & Zhang, J. (2018) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2018.1514580 · Cited by 150
“The beneficial effects of the FXR agonists as potential therapeutic agents for patients suffering from intestinal inflammation and chronic liver diseases have been demonstrated both in vivo and in vitro (Del Bas et al. 2009; Gadaleta et al. 2011).”
BackgroundThe human microbiome and bile acid metabolism: Dysbiosis, dysmetabolism, disease and intervention
Jones, M. L., Martoni, C. J., Ganopolsky, J. G., Labbé, A., & Prakash, S. (2014) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.880420 · Cited by 150
“maintenance of immune homeostasis in a mouse model of colitis [42,106].”
BackgroundClinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease
Suskind, D. L., Cohen, S. A., Brittnacher, M., Wahbeh, G. T., Lee, D. Y., Shaffer, M. L., Braly, K., Hayden, H. S., Klein, J., Gold, B. D., et al. (2017) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000000772 · Cited by 150
“Crohn’s disease A1bL1B1 3 (33) A1bL2B1 1 (11) A1bL3B1 4 (44) A2L1B1 1 (11) Ulcerative colitis”
Lajczak, N., Porru, E., Fallon, C. M., Smyth, J. S., Curley, C. E., McCarron, P. A., Tambuwala, M. M., Roda, A., & Keely, S. J. (2020) · Physiological Reports · doi:10.14814/phy2.14456 · Cited by 146
“, 2013; Ishizawa, Akagi, & Makishima, 2018; Zimber & Gespach, 2008), and each has been shown to exert protective actions in mouse models of colonic inflammation (Gadaleta et al., 2011; Ren et al., 2019; Wang et al., 2017).”
BackgroundKortner, T. M., Gu, J., Krogdahl, Å., & Bakke, A. M. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512002024 · Cited by 142
“Increased distal intestinal FXR mRNA expression may also be a direct result of the inflammation, as it has recently been demonstrated that FXR inhibits inflammation and preserves the intestinal barrier in gastrointestinal diseases((56,67)).”
BackgroundGut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease
Poeta, M., Pierri, L., & Vajro, P. (2017) · Children · doi:10.3390/children4080066 · Cited by 147
“However, patients receiving OCA show unfavorable lipid profile with increased total cholesterol and LDL and decreased high density lipoproteins (HDL), and a higher HOMA (homeostatic model assessment)-IR [112].”
BackgroundBile acids and their receptors: modulators and therapeutic targets in liver inflammation
Bertolini, A., Fiorotto, R., & Strazzabosco, M. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00935-7 · Cited by 150
New treatments and therapeutic targets for IBS and other functional bowel disorders
Simrén, M., & Tack, J. F. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0034-5 · Cited by 150
Effect of different bile acids on the intestine through enterohepatic circulation based on FXR
Xiang, J., Zhang, Z., Xie, H., Zhang, C., Bai, Y., Cao, H., Che, Q., Guo, J., & Su, Z. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1949095 · Cited by 146
“leads to decreased inhibition of inflammation, which leads to the occurrence of chronic intestinal inflammation, and may lead to the occurrence of inflammation-induced colorectal cancer.(35) FXR maintains the BA concentration in the physiological concentration range, thereby preventing the cytotoxicity induced by BAs.”
BackgroundThe gut microbiome connects nutrition and human health
Sanz, Y., Cryan, J. F., Deschasaux, M., Elinav, E., Lambrecht, R., & Veiga, P. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01077-5 · Cited by 162
“Certain gut microorganisms synthesize secondary bile acids that enhance barrier integrity in IECs through IL-18 and mucus production 114 and inhibit pro-inflammatory mononuclear phagocytes 115 by acting on farnesoid X receptor (FXR) or binding to Takeda GPCR5 (TGR5) 116 (Fig.”
Zhang, Y., Xu, Y.-W., Qi, Y., Xu, L.-N., Song, S., Yin, L., Tao, X.-F., Zhen, Y.-H., Han, X., Ma, X.-D., et al. (2017) · Toxicology · doi:10.1016/j.tox.2017.01.007 · Cited by 136
“In addition, FXR has been reported to modulate inflammatory response in liver and intestine (Zhang et al., 2009; Wang et al., 2008; Gadaleta et al., 2011), and FXR activation can inhibit NF-kB activation, whereas inflammation-induced NF-kB activation can reciprocally antagonize FXR activity (Wang…”
BackgroundChen, Y., Xiao, Y., Ge, W., Zhou, K., Wen, J., Yan, W., Wang, Y., Wang, B., Qu, C., Wu, J., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.22 · Cited by 137
How bile acids and the microbiota interact to shape host immunity
Lee, M. H., Nuccio, S.-P., Mohanty, I., Hagey, L. R., Dorrestein, P. C., Chu, H., & Raffatellu, M. (2024) · Nature Reviews Immunology · doi:10.1038/s41577-024-01057-x · Cited by 143
“TGR5 ligands similarly reduce TNF release from murine monocytes stimulated with LPS 30 and promote the differentiation of tolerogenic dendritic cells (derived from human peripheral blood monocytes) that secrete less IL-12 and TNF in response to bacterial antigens 39 .”
InfluentialBaars, A., Oosting, A., Knol, J., Garssen, J., & Van Bergenhenegouwen, J. (2015) · Microorganisms · doi:10.3390/microorganisms3040641 · Cited by 135
“to a reduced release of IFNγ, IL-17 and TNFα compared to the absence of the FXR agonist [71].”
BackgroundMethodInfluentialInterplay between bile acids and the gut microbiota promotes intestinal carcinogenesis
Wang, S., Dong, W., Liu, L., Xu, M., Wang, Y., Liu, T., Zhang, Y., Wang, B., & Cao, H. (2019) · Molecular Carcinogenesis · doi:10.1002/mc.22999 · Cited by 135
“This procedure was performed in separate groups of mice, and the concentration of FITC‐dextran in plasma was determined by comparison to a FITC‐dextran standard curve.(22)”
Pi, Y., Wu, Y., Zhang, X., Lu, D., Han, D., Zhao, J., Zheng, X., Zhang, S., Ye, H., Lian, S., et al. (2023) · Microbiome · doi:10.1186/s40168-022-01458-x · Cited by 139
“Conversely, FXR deficiency leads to heightened mucosal inflammation in mouse models of colitis [69].”
BackgroundPavlidis, P., Powell, N., Vincent, R. P., Ehrlich, S. D., Bjarnason, I., & Hayee, B. (2015) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13333 · Cited by 135
“Activation of the BA sensitive receptors appears to have a protective role in mucosal defence and hence MBF. Translation of this new knowledge into clinically relevant therapeutic interventions is eagerly awaited.”
InfluentialBile 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 138
Role of bile acids in the gut-liver axis
Schneider, K. M., Albers, S., & Trautwein, C. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.025 · Cited by 129
Man, A. W. C., Zhou, Y., Xia, N., & Li, H. (2020) · Nutrients · doi:10.3390/nu12103054 · Cited by 138
“However, other studies have suggested that pharmacological activation of FXR ameliorates inflammation and preserves the intestinal barrier integrity in two murine colitis models [164], which is also mediated by the NF-κB signaling pathway [165].”
BackgroundMicrobial Metabolites and Gut Immunology
Takeuchi, T., Nakanishi, Y., & Ohno, H. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-102035 · Cited by 143
Progress and challenges of selective Farnesoid X Receptor modulation
Massafra, V., Pellicciari, R., Gioiello, A., & van Mil, S. W. C. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.009 · Cited by 133
Self-citationGadaleta, R. M., García‐Irigoyen, O., Cariello, M., Scialpi, N., Peres, C., Vetrano, S., Fiorino, G., Danese, S., Ko, B., Luo, J., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102719 · Cited by 126
“First, FGF19 reduces the biliary and intraluminal BA levels thus reducing the detergent cytotoxic events that further increase susceptibility to intestinal inflammation in IBD patients.”
BackgroundInfluentialSelf-citationDiet, gut microbes, and the pathogenesis of inflammatory bowel diseases
Dolan, K. T., & Chang, E. B. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600129 · Cited by 136
“FXR activation in the intestine promotes antiinflammatory signaling and barrier function [75].”
BackgroundObeticholic 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
Gut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids
Liu, C., Du, M., Xie, L., Wang, W.-Z., Chen, B., Yun, C., Sun, X., Luo, X., Jiang, Y., Wang, K., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-023-01570-0 · Cited by 129
“However, the druggability and safety needs further evaluation since some studies have reported that the inhibition of intestinal FXR correlated to intestinal cancer and inflammatory bowel disease (IBD) 51,52 .”
Liu, H., Pathak, P., Boehme, S., & Chiang, J. Y. L. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m069807 · Cited by 125
“regulates intestinal innate immunity, and improves nonalcoholic fatty liver disease (6-9).”
BackgroundDisease-Associated Changes in Bile Acid Profiles and Links to Altered Gut Microbiota
Joyce, S. A., & Gahan, C. G. M. (2017) · Digestive Diseases · doi:10.1159/000450907 · Cited by 130
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 128
Farnesoid X receptor (FXR) activation and FXR genetic variation in inflammatory bowel disease
Nijmeijer, R. M., Gadaleta, R. M., van Mil, S. W. C., van Bodegraven, A. A., Crusius, J. B. A., Dijkstra, G., Hommes, D. W., de Jong, D. J., Stokkers, P. C. F., Verspaget, H. W., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023745 · Cited by 119
“We recently reported that pharmacological FXR activation decreases the severity of inflammation and preserves the intestinal barrier integrity in two well-established murine colitis models [17].”
InfluentialSelf-citationBile acids as inflammatory mediators and modulators of intestinal permeability
Calzadilla, N., Comiskey, S., Dudeja, P. K., Saksena, S., Gill, R. K., & Alrefai, W. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1021924 · Cited by 123
“A previous study utilized DSS and TNBS induced colitis in wild type and mice lacking FXR and showed that mice were treated with FXR agonist INT-747 exhibited decreased severity of colitis (55).”
MethodFatty liver diseases, bile acids, and FXR
Zhu, Y., Liu, H., Zhang, M., & Guo, G. L. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.07.008 · Cited by 122
Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review
Kimhofer, T., Fye, H. K. S., Taylor-Robinson, S. D., Thursz, M. R., & Holmes, E. C. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.38 · Cited by 117
“Some of the bile acids have also been described as versatile signalling molecules (Thomas et al, 2008, 2009; Gadaleta et al, 2011), for instance, lithocholic acid and DCA are both involved in the promotion of energy expenditure and participation in glucidic metabolism by acting on the…”
BackgroundGut microbiota and obesity: Role in aetiology and potential therapeutic target
Moran, C. P., & Shanahan, F. (2014) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2014.07.005 · Cited by 122
Bile Acids and Cancer: Direct and Environmental-Dependent Effects
Ciaula, A. D., Wang, D. Q. ‐., Molina‐Molina, E., Baccetto, R., Calamita, G., Palmieri, V. O., & Portincasa, P. (2017) · Annals of Hepatology · doi:10.5604/01.3001.0010.5501 · Cited by 119
Torres, J., de Chambrun, G. P., Itzkowitz, S. H., Sachar, D. B., & Colombel, J. F. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04753.x · Cited by 117
“Significant associations were also recognised for three non-HLA loci that had previously been established as susceptibility loci in IBD.64, 65 Interestingly, a previous study reported that a single nucleotide polymorphism (SNP) in position )308 (G fi A) in the TNFa promoter was associated with susceptibility to PSC.66…”
BackgroundInfluentialShen, H., Zhou, L., Zhang, H., Yang, Y., Jiang, L., Wu, D., Shu, H., Zhang, H., Xie, L., Zhou, K., et al. (2024) · Cell Host & Microbe · doi:10.1016/j.chom.2024.06.008 · Cited by 125
Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer
Tsuei, J., Chau, T., Mills, D. A., & Wan, Y. Y. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214538743 · Cited by 119
“Moreover, FXR agonist-treated WT mice and differentiated enterocyte-like cells displayed lower pro-inflammatory cytokines and better preserved epithelial barrier function.(40) In addition to its beneficial effects on intestinal function and inflammation, a connection between FXR and intestinal microbes was observed wh…”
BackgroundLeaky Gut and Gut-Liver Axis in Liver Cirrhosis: Clinical Studies Update
Fukui, H. (2020) · Gut and Liver · doi:10.5009/gnl20032 · Cited by 121
“FXR plays a cardinal role in protecting intestinal epithelial integrity and protecting inflammation by depression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and intestinal stimulating antimicrobial peptide release.(34,35) The FXR agonist obeticholic acid is regarded to improve…”
BackgroundBile acids as key modulators of the brain-Gut-Microbiota axis in alzheimer’s disease
Mulak, A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210608 · Cited by 114
“FXR is also a suppressor of inflammation in the liver and intestines and enhances epithelial barrier properties [41].”
BackgroundInfluentialPotent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids
Zhang, J. H., Nolan, J., Kennie, S. L., Johnston, I. M., Dew, T. K., Dixon, P. H., Williamson, C., & Walters, J. R. F. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00398.2012 · Cited by 114
“OCA enters the enterohepatic circulation (12) and thus can be used to regulate hepatic BA synthesis.”
BackgroundFarnesoid X receptor: A “homeostat” for hepatic nutrient metabolism
Massafra, V., & van Mil, S. W. C. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.10.003 · Cited by 115
Self-citationGut-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
Tissue-specific actions of FXR in metabolism and cancer
Gadaleta, R. M., Cariello, M., Sabbà, C., & Moschetta, A. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.08.005 · Cited by 112
Self-citationHan, B., Lv, X., Liu, G., Li, S., Fan, J., Chen, L., Huang, Z., Lin, G., Xu, X., Huang, Z., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2232143 · Cited by 127
“Animals lacking the nuclear receptor FXR or the membrane receptor TGR5 are more susceptible to colitis, indicating that BA-triggered receptors are essential for sustaining intestinal homeostasis.(31,32) Therefore, the stimulation of FXR/TGR5 signaling pathways through BAs can alleviate the clinical symptoms of IBD.”
BackgroundPolyunsaturated Fatty Acids in Inflammatory Bowel Diseases
Marion‐Letellier, R., Savoye, G., Beck, P. L., Panaccione, R., & Ghosh, S. K. (2013) · Inflammatory Bowel Diseases · doi:10.1097/mib.0b013e3182810122 · Cited by 110
“The synthetic FXR agonist (INT-747) ameliorates intestinal inflammation in two models of murine colitis.(36) There are numerous crosstalks between these nuclear receptors.”
BackgroundFuchs, M. A. (2011) · Journal of Lipids · doi:10.1155/2012/934396 · Cited by 108
“Subsequently novel functions of FXR have been identified including protecting the intestinal barrier and modulating the innate immunity [27, 28] and tumorigenesis [29, 30].”
Anti-inflammatory and metabolic actions of FXR: Insights into molecular mechanisms
Hollman, D. A. A., Milona, A., van Erpecum, K. J., & van Mil, S. W. C. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.07.004 · Cited by 112
Self-citationBatista, I. A., & Helguero, L. A. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0017-6 · Cited by 108
“FXR also promotes liver repair/regeneration,(111) inhibits pro-inflammatory gene expression(112,113) and cholesterol gallstone formation(114) and preserves the intestinal epithelial barrier.(113,115) FXR is a tumor suppressor that has increased liver tumor incidence in FXR-knockout in mice.”
BackgroundLiu, T., Song, X., Khan, S., Li, Y., Guo, Z., Li, C., Wang, S., Dong, W., Liu, W., Wang, B., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32563 · Cited by 108
“FXR activation reduced epithelial permeability and goblet cell loss, inhibited the production of pro-inflammatory cytokines in mouse colonic mucosa and improved the symptoms of colitis.(106) Reduction of diversity within the Firmicutes phylum was found in IBD patients, which could impair the conversion process of bile…”
BackgroundReview article: therapeutic aspects of bile acid signalling in the gut‐liver axis
Simbrunner, B., Trauner, M., & Reiberger, T. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16602 · Cited by 108
Renga, B., Mencarelli, A., Cipriani, S., D’Amore, C., Carino, A., Bruno, A. M., Francisci, D., Zampella, A., Distrutti, E., & Fiorucci, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054472 · Cited by 106
“FXR is required to maintain intestinal integrity and its deficiency results in altered intestinal permeability and tendency toward development of dysregulated immune response [15,16].”
Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy
Walters, J. R. F. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2014.32 · Cited by 104
Bile acids contribute to the development of non-alcoholic steatohepatitis in mice
Gillard, J., Clerbaux, L., Nachit, M., Sempoux, C. L., Staels, B., Bindels, L. B., Tailleux, A., & Leclercq, I. A. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100387 · Cited by 111
Iacucci, M., Santacroce, G., Majumder, S., Morael, J., Zammarchi, I., Maeda, Y., Ryan, D., Sabatino, A. D., Rescigno, M., Aburto, M. R., et al. (2024) · Gut · doi:10.1136/gutjnl-2023-331579 · Cited by 110
“77 These molecules have shown a remarkable ability to preserve intestinal epithelial and vascular intestinal barriers in IBD, preventing bacterial translocation in experimental models.”
BackgroundBile acids activated receptors in inflammatory bowel disease
Biagioli, M., Marchianò, S., Carino, A., Di Giorgio, C., Santucci, L., Distrutti, E., & Fiorucci, S. (2021) · Cells · doi:10.3390/cells10061281 · Cited by 103
“Gadaleta et al. showed that OCA significantly decreased the severity of DSS- and TNBS [54,99] e.”
BackgroundInfluentialZou, J., Shen, Y., Chen, M., Zhang, Z., Xiao, S., Liu, C., Wan, Y., Yang, L., Jiang, S., Shang, E., et al. (2020) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-020-10665-1 · Cited by 100
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 105
Intestinal secretory mechanisms and diarrhea
Keely, S. J., & Barrett, K. E. (2022) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00316.2021 · Cited by 110
Nuclear Receptors as Drug Targets in Cholestatic Liver Diseases
Halilbasic, E., Baghdasaryan, A., & Trauner, M. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2012.12.001 · Cited by 100
“specific, but were also demonstrated in intestine, where INT-747 reduced intestinal inflammation and permeability in experimental models of colitis.(86) Because bacterial overgrowth and increased intestinal permeability may play an important role in the”
BackgroundBile Acid Malabsorption in Inflammatory Bowel Disease
Vı́tek, L. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000193 · Cited by 105
“All these data are in accordance with the clinical findings demonstrating low ileal FXR activity in patients with IBD,(74) suggesting a potential therapeutic role of selective and potent FXR agonists especially those with specific intestinal tropism.(68,70,75,76) The promising therapeutic effect of obeticholic acid, a…”
ResultBile acids and colon cancer: Is FXR the solution of the conundrum?
Gadaleta, R. M., García‐Irigoyen, O., & Moschetta, A. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.002 · Cited by 98
Self-citationCariello, M., Piccinin, E., García‐Irigoyen, O., Sabbà, C., & Moschetta, A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.09.019 · Cited by 102
Self-citationBile acids: From digestion to cancers
Baptissart, M., Vega, A., Maqdasy, S., Caira, F., Baron, S., Lobaccaro, J.-M. A., & Volle, D. H. (2013) · Biochimie · doi:10.1016/j.biochi.2012.06.022 · Cited by 97
FXR Isoforms Control Different Metabolic Functions in Liver Cells via Binding to Specific DNA Motifs
Pittol, J. M. R., Milona, A., Morris, I., Willemsen, E. C. L., van der Veen, S. W., Kalkhoven, E., & van Mil, S. W. C. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.07.036 · Cited by 102
Self-citationYang, Y., Zhou, W., Wu, S., Tang, W., Wang, Z., Zhou, Z., Li, Z.-W., Huang, Q.-F., He, Y., & Zhou, H. (2021) · Endocrinology · doi:10.1210/endocr/bqab118 · Cited by 103
“Some studies have found that intestinal FXR is involved in glucose and lipid metabolism and insulin resistance and that the activation of the FXR signalling pathway can improve glucose metabolism and lipid metabolism disorders (25, 26).”
BackgroundRegulation of bile acids and their receptor FXR in metabolic diseases
Li, Y., Wang, L., Qing, Y., Luo, L., & Xiong, Y. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1447878 · Cited by 117
Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease
Wilson, A. S., Teft, W. A., Morse, B. L., Choi, Y., Woolsey, S., DeGorter, M. K., Hegele, R. A., Tirona, R. G., & Kim, R. B. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3797-3 · Cited by 97
“Furthermore, FXR, a bile acid-activated nuclear receptor, regulates the transcription of genes protective against inflammation and FXR agonists reduce the mRNA expression of pro-inflammatory proteins in mouse models of colitis [63, 64].”
BackgroundMicrobiome therapeutics for hepatic encephalopathy
Bloom, P. P., Tapper, E. B., Young, V. B., & Lok, A. S.-F. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.08.004 · Cited by 96
Song, M., Ye, J., Zhang, F., Su, H., Yang, X., He, H., Liu, F., Zhu, X., Wang, L., Gao, P., et al. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b03173 · Cited by 103
Alleviation of Gut Inflammation by Cdx2/Pxr Pathway in a Mouse Model of Chemical Colitis
Dou, W., Mukherjee, S., Li, H., Venkatesh, M., Wang, H., Kortagere, S., Peleg, A., Chilimuri, S. S., Wang, Z., Feng, Y., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036075 · Cited by 92
Vaughn, B. P., Kaiser, T., Staley, C. M., Hamilton, M. J., Reich, J., Graiziger, C. T., Singroy, S., Kabage, A. J., Sadowsky, M. J., & Khoruts, A. (2019) · Clinical and Experimental Gastroenterology · doi:10.2147/ceg.s186097 · Cited by 95
“In murine models of chemically induced colitis, activation of FXR by bile salts prevented inflammation and inhibited proinflammatory cytokines.(35) In humans, FXR activation in the small intestine is decreased in those with Crohn’s colitis as compared to those with ulcerative colitis or healthy controls.”
Inflammatory Bowel Disease Alters Intestinal Bile Acid Transporter Expression
Jahnel, J., Fickert, P., Hauer, A. C., Högenauer, C., Avian, A., & Trauner, M. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.058065 · Cited by 92
Breast Milk and Solid Food Shaping Intestinal Immunity
Parigi, S. M., Eldh, M., Larssen, P., Gabrielsson, S., & Villablanca, E. J. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00415 · Cited by 97
“Therefore, mice treated with an FXR agonist displayed a milder phenotype of inflammation during DSS-induced colitis (231, 232).”
BackgroundNuclear Receptor Control of Enterohepatic Circulation
Gonzalez, F. J. (2012) · Comprehensive physiology · doi:10.1002/cphy.c120007 · Cited by 105
“the benefit of FXR activation in the treatment of various diseases involving bile acid dysfunction, such as liver fibrosis (38) and inflammatory bowel disease (42).”
Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon
Đermadi, D., Valo, S., Ollila, S., Soliymani, R., Sipari, N., Pussila, M., Sarantaus, L., Lindén, J., Baumann, M., & Nyström, M. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2860 · Cited by 91
Bile acids affect intestinal barrier function through FXR and TGR5
Song, G., Xie, Y., Yi, L., Cheng, W., Jia, H., Shi, W., Liu, Q., Fang, L., Xue, S., Liu, D., et al. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1607899 · Cited by 111
FXR modulators for enterohepatic and metabolic diseases
Wang, H., He, Q., Wang, G., Xu, X., & Hao, H. (2018) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2018.1527906 · Cited by 90
“Additionally, OCA treatment protected mice from chemical-induced intestinal inflammation, as shown by reduction of body weight loss, epithelial permeability, rectal bleeding, colonic shortening, ulceration, inflammatory cell infiltration and goblet cell loss [123], providing evidence for potential use of FXR agonists…”
BackgroundThe microbiota-gut-brain axis: Focus on the fundamental communication pathways
Bistoletti, M., Bosi, A., Banfi, D., Giaroni, C., & Baj, A. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.08.012 · Cited by 91
Bile acid-based therapies for non-alcoholic steatohepatitis and alcoholic liver disease
Li, T., & Chiang, J. Y. L. (2020) · HepatoBiliary Surgery and Nutrition · doi:10.21037/hbsn.2019.09.03 · Cited by 87
“FXR activation also antagonizes NF-κB-stimulated inflammation in liver (126) and preserves the intestinal barrier function in inflammatory bowel disease (127).”
BackgroundBurke, K. E., D’Amato, M., Ng, S. C., Pardi, D. S., Ludvigsson, J. F., & Khalili, H. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00273-2 · Cited by 93
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 107
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 89
Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis
Massafra, V., Ijssennagger, N., Plantinga, M., Milona, A., Pittol, J. M. R., Boes, M. L., & van Mil, S. W. C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.11.001 · Cited by 85
Self-citationHuman Postprandial Nutrient Metabolism and Low-Grade Inflammation: A Narrative Review
Meessen, E. C. E., Warmbrunn, M. V., Nieuwdorp, M., & Soeters, M. R. (2019) · Nutrients · doi:10.3390/nu11123000 · Cited by 95
Correlation of fecal metabolomics and gut microbiota in mice with endometriosis
Ni, Z., Sun, S., Bi, Y., Ding, J., Cheng, W., Yu, J., Zhou, L., Li, M., & Yu, C. (2020) · American Journal of Reproductive Immunology · doi:10.1111/aji.13307 · Cited by 88
FXR silencing in human colon cancer by DNA methylation and KRAS signaling
Bailey, A. M., Zhan, L., Maru, D. M., Shureiqi, I., Pickering, C. R., Kiriakova, G. M., Izzo, J. G., He, N., Wei, C., Baladandayuthapani, V., et al. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00234.2013 · Cited by 85
Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives
Li, M., Yang, L., Mu, C., Sun, Y., Gu, Y., Chen, D., Liu, T., & Cao, H. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.03.038 · Cited by 89
“As one of the receptors of SBAs, the activation of FXR in small intestine has been proved to inhibit bacterial overgrowth and translocation[122], and then ameliorate intestinal inflammation [130].”
BackgroundCholestatic liver diseases: new targets, new therapies
Santiago, P., Scheinberg, A. R., & Levy, C. (2018) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756284818787400 · Cited by 85
Soderborg, T. K., Borengasser, S. J., Barbour, L. A., & Friedman, J. E. (2016) · Diabetologia · doi:10.1007/s00125-016-3880-0 · Cited by 84
“The beneficial effects of BA signalling via FXR and TGR5 also include attenuation of proinflammatory innate immune responses in a mouse model of NAFLD [85], lipopolysaccharide (LPS)-induced hepatic damage and inflammation [86] and inflammatory bowel disease [87].”
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
