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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.
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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 501–600 of 875
Wang, M., Zhang, Y., Tong, Y., Guo, P., Zhang, J., Wang, C., & Gao, Y.-Y. (2022) · Poultry Science · doi:10.1016/j.psj.2022.102191 · Cited by 20
Hu, J., Hou, Q., Zheng, W., Yang, T., & Yan, X. (2023) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2200439 · Cited by 20
“Therefore, L. gasseri LA39 may be a potential probiotic used to prevent IBD via promoting the bio‐ synthesis of primary BAs, as demonstrated in our study.”
BackgroundDai, M., Wan, P., Lin, L., Wu, Z. E., Zhang, T., Zhao, Q., Cheng, Y., Lin, Q., Zhang, B., Liu, A., et al. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.155054 · Cited by 19
Farnesoid X receptor: a potential therapeutic target in multiple organs.
Zhang, C., Wang, Z., Feng, Q., Chen, W.-D., & Wang, Y.-D. (2021) · Histology and Histopathology · doi:10.14670/hh-18-301 · Cited by 16
Anti-Cholestatic Therapy with Obeticholic Acid Improves Short-Term Memory in Bile Duct-Ligated Mice
Gee, L. M. V., Barron-Millar, B., Leslie, J., Richardson, C., Zaki, M. Y. W., Luli, S., Burgoyne, R. A., Cameron, R. I. T., Smith, G. R., Brain, J. G., et al. (2023) · The American Journal of Pathology · doi:10.1016/j.ajpath.2022.09.005 · Cited by 18
Nutrient acquisition of gut microbiota: Implications for tumor immunity
Wang, Y., Huang, J., Tong, H., Jiang, Y., Yu, J., & Ma, X. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.06.003 · Cited by 19
The gut microbiota and its metabolites: novel therapeutic targets for inflammatory bowel disease
Shen, X. Z., Li, Y., Wang, D., & Sun, K. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1690279 · Cited by 25
Lazarenko, V. A., Чурилин, М. И., Azarova, I. E., Klyosova, E. Y., Быканова, М. А., Ob'edkova, N., Churnosov, M. I., Bushueva, O. Y., Маль, Г. С., Povetkin, S. V., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10020259 · Cited by 21
“Furthermore, an in silico predicted transcription factor NR1H4 is known to impact the expression of cytokine genes underlying inflammatory mechanisms of atherosclerosis [76].”
BackgroundPlasminogen Activator Inhibitor-1 Potentiates Neutrophil Infiltration and Tissue Injury in Colitis
Wang, X., Li, G., Huang, J., Jiang, S., Li, N., Mu, H., & Xu, C. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.75890 · Cited by 18
“The histological scores were ranked by combining the scoring system for colitis-associated histological changes [52] and goblet cell loss [53] as follows: 0 (no evidence of inflammation); 1 (low level of inflammation with scattered infiltrating mononuclear cells, 1–2 foci); 2 (moderate inflammation with multiple foci)…”
MethodLu, Z., Hsu, C., Younis, N. K., Mustafa, M. A., Matveeva, E. A., Al-Juboory, Y. H. O., Adil, M., Athab, Z. H., & Abdulraheem, M. N. (2024) · Apmis · doi:10.1111/apm.13401 · Cited by 19
The role of the gut microbiome in graft fibrosis after pediatric liver transplantation
Qin, T., Fu, J., & Verkade, H. J. (2020) · Human Genetics · doi:10.1007/s00439-020-02221-8 · Cited by 18
Dai, X., He, L., Hu, N., Guo, C., Zhou, M., Zhao, X., Wang, C., Gong, L., Ma, C., Xue, X., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.734670 · Cited by 18
Sun, L. Y., Yang, N., Liu, Z., Ye, X., Cheng, M., Deng, L., Zhang, J., Wu, J., Shi, M., & Liao, W. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01052-3 · Cited by 19
“OCA successfully decreased pro-inflammatory cytokine production and preserved epithelial barrier function in DSS-and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse models [51].”
BackgroundHan, Y., Guo, X., Du, H., Guo, Y., Ding, Q., Li, F., Meng, Y., & Xiao, H. (2025) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2025.105075 · Cited by 20
Liu, A., Huang, M., Xi, Y., Deng, X., & Xu, K. (2025) · Biomedicines · doi:10.3390/biomedicines13061422 · Cited by 17
Microbial bile acid modifications: current understandings, key problems, and future perspectives
Zhang, H., Wen, J., Liu, X., Feng, Y., Liu, X., & Ning, K. (2025) · Science China Life Sciences · doi:10.1007/s11427-025-3019-2 · Cited by 20
“…reported that FXR, a nuclear receptor of BAs, can activate intestinal protective gene expression and inhibit bacterial overgrowth in the ileum, thus preventing epithelial deterioration and bacterial translocation in patients with impaired bile flow (Gadaleta et al., 2011; Inagaki et al., 2006).”
Zhang, S., Zhao, X., He, X., Shi, W., & Ma, N. (2026) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-025-01319-1 · Cited by 20
“In FLHS, reduced FXR signaling in both the liver and intestine leads to gut microbiota dysbiosis (lower Ruminococcus and higher Desulfovibrio ), intestinal permeability increased, and BA metabolism and gut leakiness worsened [78, 79].”
Chyme Reinfusion Restores the Regulatory Bile Salt–FGF19 Axis in Patients With Intestinal Failure
Koelfat, K. V. K., Picot, D., Chang, X., Desille‐Dugast, M., van Eijk, H. M. H., van Kuijk, S. M. J., Leníček, M., Layec, S., Carsin, M., Dussaulx, L., et al. (2021) · Hepatology · doi:10.1002/hep.32017 · Cited by 17
Mooranian, A., Foster, T., Ionescu, C. M., Walker, D., Jones, M., Wagle, S. R., Kovačević, B., Chester, J., Johnston, E., Wong, E. Y. M., et al. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13081184 · Cited by 17
“In the case of murine models of inflammatory bowel disease, TNF-α production was attenuated by the activation of the FXR receptor, in which CDCA is a potent agonist [77].”
BackgroundNew Kids on the Block: Bile Salt Conjugates of Microbial Origin
Ay, Ü., Leníček, M., Claßen, A., Damink, S. W. M. O., Bolm, C., & Schaap, F. G. (2022) · Metabolites · doi:10.3390/metabo12020176 · Cited by 18
“, Gram-negative bacteria such as Salmonella enterica or Escherichia coli is expression of efflux pumps that maintain low levels of bile salts inside bacteria [48,49].”
BackgroundClinical significance and oncogenic function of NR1H4 in clear cell renal cell carcinoma
Huang, S., Hou, Y., Hu, M., Hu, J., & Liu, X. (2022) · BMC Cancer · doi:10.1186/s12885-022-10087-4 · Cited by 16
“NR1H4 involved in several biological processes, including lipogenesis, gluconeogenesis, ammonia detoxification, glycogen synthesis, bile acid metabolism and inflammation [7, 8].”
BackgroundXing, L., Zhang, Y., Li, S., Tong, M., Bi, K., Zhang, Q., & Li, Q. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054258 · Cited by 17
“When liver organic solute transporter-alpha/beta (OSTα/OSTβ) expression is downregulated, abnormal retention of BAs in hepatocytes within the organism occurs, leading to chronic liver injury [12], while patients diagnosed with HCC between 13 and 52 months concerning bile acid transporter deficiency resulted in a suppr…”
BackgroundSelective bowel decontamination improves the survival of 90% hepatectomy in rats
Ren, W., Wang, X., Zhang, A., Li, C., Chen, G., Ge, X., Pan, K., & Dong, J. (2015) · Journal of Surgical Research · doi:10.1016/j.jss.2015.01.024 · Cited by 17
Obeticholic acid for the treatment of primary biliary cirrhosis
Jones, D. E. (2016) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2016.1216784 · Cited by 18
Dietary and metabolic modulators of hepatic immunity
Carambia, A., & Herkel, J. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0659-4 · Cited by 17
Nijmeijer, R. M., Schaap, F. G., Smits, A. J. J., Kremer, A. E., Akkermans, L. M. A., Kroese, A. B. A., Rijkers, G. T., Schipper, M. E. I., Verheem, A., Wijmenga, C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114393 · Cited by 17
“In the second experiment, intestinal permeability was assessed with fluorescein isothiocyanate (FITC)-conjugated dextran as previously described [15].”
Self-citationYalchin, M., Segal, J. P., Mullish, B. H., Quraishi, M. N., Iqbal, T. H., Marchesi, J. R., & Hart, A. L. (2019) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756284819891038 · Cited by 17
What's eating you? An update on Giardia, the microbiome and the immune response
Singer, S. M., Angelova, V. V., DeLeon, H., & Miskovsky, E. (2020) · Current Opinion in Microbiology · doi:10.1016/j.mib.2020.09.006 · Cited by 17
Wang, A., Yang, X., Lin, J., Wang, Y., Yang, J., Zhang, Y., Tian, Y., Dong, H., Zhang, Z., & Song, R. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118715 · Cited by 16
Ma, Y., Yang, H., Wang, X., Huang, Y., Li, Y., & Pan, G. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118968 · Cited by 18
Biological functions and pharmacological behaviors of bile acids in metabolic diseases
Zhuang, T., Wang, X., Wang, Z., Gu, L., Yue, D., Wang, Z., Li, X., Yang, L., Huang, W., & Ding, L. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.11.003 · Cited by 23
Farnesoid X Receptor Expression in Microscopic Colitis: A Potential Role in Disease Etiopathogenesis
Torres, J., Palmela, C., de Sena, P. G., Santos, M. P. C., Gouveia, C. F., Oliveira, M. H., Henriques, A. R., Rodrigues, C. M. P., Cravo, M. L., & Borralho, P. (2017) · GE Portuguese Journal of Gastroenterology · doi:10.1159/000481197 · Cited by 16
Azizsoltani, A., Niknam, B., Taghizadeh-Teymorloei, M., Ghoodjani, E., Dianat-Moghadam, H., & Alizadeh, E. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118249 · Cited by 15
Impact of Gut Microbiome on Gut Permeability in Liver and Gut Diseases
Saha, P., & Hartmann, P. (2025) · Microorganisms · doi:10.3390/microorganisms13061188 · Cited by 16
“Similarly, FXR activation by the agonist INT-747 protected the intestinal barrier, increased goblet cell function, and prevented colon shortening in the dextran sodium sulfate-treated colitis model [217].”
Bile acid modulation of host immunity
Anh, N. B., Yang, X., & Hang, H. C. (2025) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.70014 · Cited by 16
FXR-targeted drug discovery: Recent advances and therapeutic perspectives
Li, Q., Liu, Z., Shang, W., Zhou, X., Mao, W., Cao, Y., & Shan, L. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118332 · Cited by 19
Sex differences feed into nuclear receptor signaling along the digestive tract
Dean, A. E., Reichardt, F., & Anakk, S. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166211 · Cited by 14
Discovery of LH10, a novel fexaramine-based FXR agonist for the treatment of liver disease.
Huang, W., Cao, Z.-J., Wang, W.-X., Yang, Z.-C., Jiao, S.-X., Chen, Y., Chen, S.-L., Zhang, L.-Y., & Li, Z. (2024) · Bioorganic chemistry (Print) · doi:10.1016/j.bioorg.2023.107071 · Cited by 15
Zhang, N.-N., Liu, J., Guo, X., Li, S., Wang, F., & Wang, M. (2021) · Nutrients · doi:10.3390/nu13113926 · Cited by 15
Zhang, C., Gan, Y., Lv, J.-W., Qin, M.-Q., Hu, W., Liu, Z.-B., Ma, L., Song, B., Li, J., Jiang, W., et al. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106442 · Cited by 15
Chiang, J. Y. L. (2014) · Hepatology · doi:10.1002/hep.27616 · Cited by 15
“and FXR agonists had an anti-inflammatory function through the inhibition of nuclear factor-jB (NFjB)– mediated inflammatory cytokine production in hepatocytes and enterocytes.(3,4) However, how FXR signaling inhibits NF-jB activity is not clear.”
BackgroundKe, L., Li, C., Men, J., Xu, B., Yang, C., Yan, P., Gai, Z., Zhang, Q., & Zhang, L. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1409128 · Cited by 15
Targeting Bile-Acid Metabolism: Nutritional and Microbial Approaches to Alleviate Ulcerative Colitis
Jiang, X., Ren, J., Yu, G., Wu, W., Chen, M., Zhao, Y., & He, C. (2025) · Nutrients · doi:10.3390/nu17071174 · Cited by 16
“Gadaleta et al., 2011 [79] FXR activation inhibits the secretion of TNF-α in immune cells (such as PBMCs and CD14 + monocytes).”
FXR inhibition functions as a checkpoint blockade of the pathogenic Tfh cell response in lupus
Wang, X., Ye, L., Liu, S., Zheng, Y., Zhu, L., Huang, W., Song, J., Shao, J., Wu, F., Zhang, C., et al. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01309-3 · Cited by 14
Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy
Ding, S., Lei, Y., Zhao, Z., Li, X., Lang, J., Zhang, J., Li, Y., Zhang, C., & Dai, D. (2025) · Comprehensive physiology · doi:10.1002/cph4.70042 · Cited by 15
“Gadaleta et al. reported that FXR activation reduced goblet cell loss, decreased intestinal permeability, and alleviated intestinal inflammation to improve inflammatory bowel disease (IBD) prognosis (Gadaleta et al. 2011).”
Chen, X., Dai, P., Zhu, Y., Jin, W., Xie, Y., Yang, Z., Wang, Z., Jin, X., Lei, M., Shi, L., et al. (2025) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2025.124716 · Cited by 16
Feng, M., Zhou, Y., Gao, Z., Huang, W., Xie, W., Xie, W., Liu, Z., Tang, S., Xiong, X., Chen, Y., et al. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.117885 · Cited by 14
Xiao, Y., Jia, Y., Liu, W., Niu, C., Mai, Z., Dong, J., Zhang, X.-S., Yuan, Z., Ji, P., Wei, Y., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1399829 · Cited by 14
Li, J., Liu, H., Hu, X., Zhang, S., Yu, Q., Kuang, G., Liu, L., Yu, D., Huang, J., Xia, Y. F., et al. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113087 · Cited by 16
Li, K., Feng, C., Chen, H., Feng, Y., & Li, J. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.880553 · Cited by 14
“FXR activation inhibits the production of intestinal inflammatory factors and maintains the integrity of the intestinal epithelial barrier (31).”
BackgroundRecent updates on targeting the molecular mediators of NAFLD
Wang, J., Wang, L., Zhang, X., Zhang, P., Cai, J., She, Z., & Li, H. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02282-4 · Cited by 13
Maselli, K. M., Gee, K. M., Isani, M. A., Fode, A. M., Schall, K. A., & Grikscheit, T. C. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00119.2020 · Cited by 14
Genetic variation in the farnesoid X-receptor predicts Crohn’s disease severity in female patients
Wilson, A. S., Wang, Q., Almousa, A. A., Jansen, L. E., Choi, Y., Schwarz, U. I., & Kim, R. B. (2020) · Scientific Reports · doi:10.1038/s41598-020-68686-9 · Cited by 14
Baldi, S., Turrini, M., Cei, F., Menicatti, M., Bartolucci, G., & Amedei, A. (2026) · BioFactors · doi:10.1002/biof.70078 · Cited by 13
“In the intestine, OCA enhances mucosal barrier integrity and attenuates inflammation, providing protection in experimental colitis models [38].”
InfluentialBile acid alterations associated with indolent course of inflammatory bowel disease
Liu, C., Zhan, S., Li, N., Tu, T., Lin, J., Li, M., Chen, M., Zeng, Z., & Zhuang, X. (2023) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2023.2200518 · Cited by 13
“What’s more, activating FXR by its agonists or intestinal fungus Candida metapsilosis M2006B had been reported to maintain a competent barrier and improve colitis by regulating dysbiosis in recent studies, indicating FXR as a promising therapeutic target for IBD [51,52] Researchers have identified a reduction of isoLC…”
BackgroundLuo, L., Zhao, Y., Zhang, G., Dong, S., Xu, Y.-Y., Shi, H., Zhang, M., Liu, X., Wang, S., Luo, H., et al. (2024) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.123.002020 · Cited by 14
GÜVEY, H., Çelik, S., Çalışkan, C. S., Yılmaz, Z., Yılmaz, M., Erten, Ö., & Tinelli, A. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182312555 · Cited by 13
“Bile acids regulate cholesterol, glucose metabolism, and intestinal epithelial barrier characteristics via farnesoid X receptors (FXR) and shape intestinal microbiota [5,6].”
BackgroundDawson, P. A. (2015) · Elsevier eBooks · doi:10.1016/b978-0-444-63438-2.00012-2 · Cited by 13
Perrigoue, J., Das, A., & Mora, J. R. (2014) · Nestlé Nutrition Institute Workshop series · doi:10.1159/000360685 · Cited by 13
Cheng, L., Tian, F., Tian, F., Tang, L., Chen, G., Luo, Z., Ren, J., & Wang, S. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12479 · Cited by 13
Gao, L., Zheng, H., Zhao, Q., Wang, Y., He, Y., Hou, C., Yang, N., Liang, K., Meng, W., He, X., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02384-8 · Cited by 17
Current insights in molecular characterization of non-alcoholic fatty liver disease and treatment
Che, W., Zhao, M., Li, X., Li, C., Cho, W. C. S., & Yu, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1002916 · Cited by 12
“Activation of the farnesoid X receptor can reduce fibrosis and inflammation in NASH by regulating bile acid metabolism (Figure 4) (105, 106).”
BackgroundSafari, F., Sharifi, M., Talebi, A., Mehranfard, N., & Ghasemi, M. (2023) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-023-02455-z · Cited by 12
Briggs, K., Tomar, V., Ollberding, N. J., Haberman, Y., Bourgonje, A. R., Hu, S., Chaaban, L., Sunuwar, L., Weersma, R. K., Denson, L. A., et al. (2024) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izae003 · Cited by 12
Patented Farnesoid X receptor modulators: a review (2019 – present)
Gioiello, A., Rosatelli, E., & Cerra, B. (2024) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2024.2314296 · Cited by 12
Clinical Aspects of Gut Microbiota in Hepatocellular Carcinoma Management
Xu, J., Zhan, Q., Fan, Y., Lo, E. K. K., Zhang, F., Yu, Y., El-Nezami, H. S., & Zeng, Z. (2021) · Pathogens · doi:10.3390/pathogens10070782 · Cited by 14
“FXR, a nuclear receptor, activation is involved in regulating antibacterial defense in the small intestine [32], preventing chemically induced intestinal inflammation [33] and modulating liver regeneration [34].”
BackgroundMechanisms of gastrointestinal barrier dysfunction in COVID-19 patients
Xue, W., Honda, M., & Hibi, T. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i15.2283 · Cited by 12
Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury
Jain, A. K., & Teckman, J. H. (2014) · Advances in Hepatology · doi:10.1155/2014/621380 · Cited by 12
“Mice lacking FXRhave compromised gut permeability on fluorescein isothiocyanate- (FITC-) conjugated dextran assay [56].”
Wang, X., Li, S., Chen, M., Liu, J., Dong, R.-R., Wang, H.-M., & Zhu, S.-G. (2017) · Shock · doi:10.1097/shk.0000000000001019 · Cited by 9
Panek-Jeziorna, M., & Mulak, A. (2020) · Gastroenterology Research and Practice · doi:10.1155/2020/2389312 · Cited by 11
“The results of both in vivo and in vitro studies have demonstrated that on the one hand, inflammation reduces FXR expression, while on the other hand, the activation of FXR exerts antiinflammatory effect by reducing the production of proinflammatory cytokines [35].”
BackgroundWang, Y., Zheng, L., Zhou, Z., Yao, D., Huang, Y., Liu, B., Duan, Y., & Li, Y. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16676 · Cited by 12
Bourgonje, A. R., Bolte, L. A., Vranckx, L. L. C., Spekhorst, L. M., Gaćeša, R., Hu, S., van Dullemen, H. M., Visschedijk, M. C., Festen, E. A. M., Samsom, J. N., et al. (2022) · Nutrients · doi:10.3390/nu14122522 · Cited by 11
“Similarly, experimental work indicated that FXR activation could attenuate chemically induced intestinal inflammation, restore intestinal barrier integrity, inhibit the production of pro-inflammatory cytokines and reduce the loss of goblet cells in mice, fuelling the rationale for exploring FXR agonists as therapeutic…”
Yu, S., Zhang, M., Ye, Z., Wang, Y., Wang, X., & Chen, Y. (2023) · Cell Regeneration · doi:10.1186/s13619-022-00143-6 · Cited by 11
“*Correspondence: ygchen@tsinghua.edu.cn healthy control tissues of IBD patients, such as NF-κB, TNF-α, immune response, proinflammatory cytokines, and chemokines (Allen et al. 2012, Gadaleta et al. 2011).”
BackgroundCanovai, E., Farré, R., Accarie, A., Lauriola, M., Hertogh, G. D., Vanuytsel, T., Pirenne, J., & Ceulemans, L. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914881 · Cited by 11
“FXR agonists have been shown to reduce intestinal inflammation by inhibiting the NF-κB pathway, resulting in reduced structural damage [9].”
BackgroundInfluentialGut–Brain Crosstalk and the Central Mechanisms of Orofacial Pain
Tao, R., Liu, S., Crawford, J. A., & Tao, F. (2023) · Brain Sciences · doi:10.3390/brainsci13101456 · Cited by 11
Potential role of bile acids in the pathogenesis of necrotizing enterocolitis
Yang, J., Chen, X., Liu, T., & Shi, Y. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122279 · Cited by 11
Yang, J., Ma, G., Wang, K., Yang, H., Jiang, S., Fan, Q., Zhou, X., Guo, G., & Han, Y. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1342119 · Cited by 11
“Finally, bile acids can also serve as raw materials for gut microbiota to promote the proliferation of some bacteria (42, 43).”
BackgroundPrebiotic inulin ameliorates SARS-CoV-2 infection in hamsters by modulating the gut microbiome
Song, I., Yang, J., Saito, M., Hartanto, T., Nakayama, Y., Ichinohe, T., & Fukuda, S. (2024) · npj Science of Food · doi:10.1038/s41538-024-00248-z · Cited by 12
Hai, L., Wu, J., Pan, X., Yin, W., & Wu, Z. (2025) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.70084 · Cited by 11
Wang, T., Chen, J., Shu, C., Shen, X., Fu, Y., Li, M., & Luo, Z. Y. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.01.049 · Cited by 11
Saccharomyces boulardii Alleviates Colitis by Regulating FXR-NLRP3 Mediated Macrophage Pyroptosis
Yang, L., Li, W., Zhao, Q., Mo, Q., Liu, T., & Cao, H. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s504957 · Cited by 12
“7,8 Increasing evidence indicates the involvement of FXR in IBD.”
Li, M., Wang, F., Zhang, C., Li, M.-A., Wang, T., Li, Y.-C., & Fu, F.-H. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115627 · Cited by 11
Remodeling of the Gut Microbiota in Colorectal Cancer and its Association with Obesity
Damavandi, S., Avan, A., Zafari, N., Velayati, M., Mehrabadi, S., Khazaei, M., Hassanian, S. M., & Ferns, G. A. (2023) · Current Pharmaceutical Design · doi:10.2174/1381612829666230118123018 · Cited by 11
The Role of the Gastrointestinal Microbiome in Liver Disease
Shalaby, N., Samocha‐Bonet, D., Kaakoush, N. O., & Danta, M. (2023) · Pathogens · doi:10.3390/pathogens12091087 · Cited by 11
Animal models of biliary tract injury
Österreicher, C. H., & Trauner, M. A. (2012) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32835264d9 · Cited by 11
“Autoimmunity [e.g. primary biliary cirrhosis (PBC), immunemediated biliary tract injury, primary sclerosing cholangitis (PSC), obstruction (tumors compressing bile ducts or bile duct stones)], and ingestion of xenobiotics (pharmaceuticals as well as household detergents and several chemicals) are frequent causes of ch…”
BackgroundInfluentialJones, M. L., Martoni, C., Ganopolsky, J. G., Sulemankhil, I., Ghali, P., & Prakash, S. (2013) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2013.833601 · Cited by 11
Miyazaki, T., Honda, A., Ikegami, T., Iida, T., & Matsuzaki, Y. (2018) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.18-80 · Cited by 11
Hao, Q., Huang, F., Chang, L., Dai, H., Chen, W., Yao, Y., & Zhen, Y.-H. (2025) · mSystems · doi:10.1128/msystems.00288-25 · Cited by 11
“The study demonstrated that activation of FXR in inflammatory bowel disease inhibits the NF-κB pathway in the gut (33).”
Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome
Hou, L., Wang, H., Yan, M., Cai, Y., Zheng, R., Ma, Y., Tang, W., & Jiang, W. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167221 · Cited by 11
Gut microbiome composition and dysbiosis in immune thrombocytopenia: A review of literature
Saki, N., Hadi, H., Keikhaei, B., Mirzaei, A., & Purrahman, D. (2024) · Blood Reviews · doi:10.1016/j.blre.2024.101219 · Cited by 10
Nuclear receptors behind the therapeutic effects of plant sterols on metabolism: A review
Brañes, M. C., Gillet, R., & Valenzuela, R. B. (2024) · Lipids · doi:10.1002/lipd.12409 · Cited by 11
FXR protects against neonatal sepsis by enhancing the immunosuppressive function of MDSCs
He, J., Zhang, Y., Jing, Y., Dong, R., Li, T., Zheng, X., Zhou, P., Shi, K., Zhong, W., Liu, Q., et al. (2025) · Cellular and Molecular Immunology · doi:10.1038/s41423-025-01289-4 · Cited by 10
Li, P., Lei, Q., Yu, X., Shen, Y., Chen, Y., Hou, C., Hu, B., Cui, Y., Liu, Z., Qin, Y., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-334565 · Cited by 10
“38 BAs can alter the diversity of gut microbiota composition and provide sufficient energy to support the diversity of many micro-organisms.”
Achenbach, J., Gabler, M., Steri, R., Schubert‐Zsilavecz, M., & Proschak, E. (2013) · MedChemComm · doi:10.1039/c3md00049d · Cited by 10
Bile Acids in Control of the Gut-Liver-Axis
Hild, B., Heinzow, H. S., Schmidt, H., & Maschmeier, M. (2021) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1330-9644 · Cited by 10
“[49] Gadaleta RM, van Erpecum KJ, Oldenburg B et al.”
BackgroundShibuya, N., Higashiyama, M., Akita, Y., Shirakabe, K., Ito, S., Nishii, S., Mizoguchi, A., Inaba, K., Tanemoto, R., Sugihara, N., et al. (2021) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15509 · Cited by 10
Cariello, M., Zerlotin, R., Pasculli, E., Piccinin, E., Peres, C., Porru, E., Roda, A., Gadaleta, R. M., & Moschetta, A. (2022) · Cancers · doi:10.3390/cancers14133081 · Cited by 11
“Pharmacological targeting of FXR by the semi-synthetic BA Obeticholic acid, a drug that is already in clinical for the treatment of primary biliary cholangitis (PBC), has been shown to counteract the intestinal inflammatory response in chemically-induced murine models of colitis, beneficial effects that are absent in…”
BackgroundSelf-citationNovel Therapies on Primary Biliary Cirrhosis
Czul, F., & Levy, C. (2015) · Clinics in Liver Disease · doi:10.1016/j.cld.2015.08.006 · Cited by 10
“Therefore, by activating FXR, OCA reduces production of bile in the liver and increases bile flow in cholestatic conditions, thus protecting the hepatocytes from accumulation of cytotoxic bile acids.(21)”
BackgroundŁukawska, A., & Mulak, A. (2024) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/184132 · Cited by 10
Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta‐Analyses
Zhu, C., Han, Y., Byun, J., Xiao, X., Rothwell, S., Miller, F. W., Lundberg, I. E., Gregersen, P. K., Vencovský, J., Shaw, V. R., et al. (2024) · Arthritis & Rheumatology · doi:10.1002/art.43088 · Cited by 9
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
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