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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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“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 601–700 of 875
Xiao, T., Yu, Z., Yang, H., You, J., & Wu, X. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.114722 · Cited by 9
Zhang, P., Xu, S., Li, N., & Yu, C. (2025) · Digestive Diseases and Sciences · doi:10.1007/s10620-025-09176-8 · Cited by 9
“Furthermore, in FXR-deficient mouse models, aggravated intestinal inflammation has been observed, whereas FXR activation preserves epithelial integrity, prevents bacterial translocation, and modulates mucosal immunity [13–15].”
Liu, S., Liang, Z., Zhu, L., Zheng, Y., Yu, H., Ye, S., Liang, T., Huang, L., Ouyang, J., Cao, Y., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-012259 · Cited by 9
“…mechanism of tumor antigen-specific CD8 + T-cell exhaustion in ICC and demonstrates that pharmacological inhibition of FXR with UDCA revitalizes anti-tumor immunity and synergizes with PD-L1 blockade, presenting a readily translatable therapeutic strategy to overcome immunotherapy resistance.”
He, X., Xu, Z., Wang, B., Zheng, Y.-R., Gong, W., Huang, G., Zhang, L., Li, Y., & He, F. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.08.020 · Cited by 9
Koelfat, K. V. K., Visschers, R. G. J., Hodin, C. M. I. M., de Waart, D. R., van Gemert, W. G., Cleutjens, J. P. M., Gijbels, M. J., Shiri‐Sverdlov, R., Mookerjee, R. P., Lenaerts, K., et al. (2017) · Journal of Clinical and Translational Research · doi:10.18053/jctres.03.201703.004 · Cited by 9
“The farnesoid x receptor (FXR) is a bile salt-sensing transcription factor that plays a key role in the regulation of bile salt synthesis, lipid and carbohydrate metabolism, and is required for maintaining intestinal integrity and limiting toxic effects of bile salts [8,9].”
BackgroundPathophysiology of reflux oesophagitis: role of Toll-like receptors 2 and 4 and Farnesoid X receptor
Nortunen, M., Väkiparta, N., Porvari, K., Saarnio, J., Karttunen, T. J., & Huhta, H. I. (2021) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-021-03066-w · Cited by 9
Wang, M., Huang, Y., Xin, M., Li, T., Wang, X., Fang, Y., Liang, S., Cai, T., Xu, X., Dong, L., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1156471 · Cited by 11
Zhou, Y.-W., Ren, Y., Lu, M., Xu, L., Cheng, W.-X., Zhang, M., Ding, L.-P., Chen, D., Gao, J., Du, J., et al. (2024) · World Journal of Gastroenterology · doi:10.3748/wjg.v30.i1.34 · Cited by 10
“More importantly, PBT to MLNs[20,32] and mesenteric adipose tissue[20,33] as well as defects in dendritic cell (DC) migration[33,34] have been described in CD.”
Chen, C., Xu, J., Han, T., Chen, G., Yu, K., Du, C., Shen, W., Sun, Y., & Zeng, X. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c07733 · Cited by 9
Zhang, X., Ma, L., Shen, Y., Zhang, C., Hou, B., & Zhou, Y. (2021) · Bioengineered · doi:10.1080/21655979.2021.2012549 · Cited by 9
“The intestinal epithelium is composed of a layer of epithelial cells and is a crucial part of the intestinal mucosal barrier [25].”
BackgroundRetractedFallon, C. M., Smyth, J. S., Quach, A., Lajczak, N., O’Toole, A., Barrett, K. E., Sheridan, H., & Keely, S. J. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102569 · Cited by 9
“Several studies have shown that FXR activation promotes colonic epithelial barrier function (8-14), an effect that likely contributes to its actions in preventing intestinal inflammation in various murine models of disease (14-16).”
BackgroundImmunoregulatory Functions of Nuclear Receptors: Mechanisms and Therapeutic Implications
Zhao, L., Gimple, R. C., Yang, Z., Wei, Y., Gustafsson, J.-Α., & Zhou, S. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.10.002 · Cited by 9
FXR Friend-ChIPs in the Enterohepatic System
Meadows, V., Yang, Z., Basaly, V., & Guo, G. L. (2023) · Seminars in Liver Disease · doi:10.1055/a-2128-5538 · Cited by 8
“Further, FXR promotes epithelial layer integrity following activation through increased intestinal tight junction protein expression (22) and mucus production (23).”
BackgroundInfluentialWang, Y., Chen, J., Tang, J., Xiao, J., Zheng, Y., Tang, L., & Luo, H. (2021) · Scientific Reports · doi:10.1038/s41598-021-84694-9 · Cited by 8
Heering, J., Jores, N., Kilu, W., Schallmayer, E., Peelen, E., Muehler, A. R., Kohlhof, H., Vitt, D., Linhard, V. L., Gande, S. L., et al. (2022) · ACS Chemical Biology · doi:10.1021/acschembio.2c00599 · Cited by 8
Smyth, J. S., Truong, J. K., Rao, A., Lin, R., Foulke-Abel, J. D., Adorini, L., Donowitz, M., Dawson, P. A., & Keely, S. J. (2023) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00099.2023 · Cited by 8
Self-citationXu, Z., Huang, G., Gong, W., Zhao, Y., Zhou, P., Zeng, Y., & He, F. (2012) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2012.0008 · Cited by 8
Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis
Patikorn, C., Veettil, S. K., Phisalprapa, P., Pham, T. A., Kowdley, K. V., & Chaiyakunapruk, N. (2021) · Annals of Hepatology · doi:10.1016/j.aohep.2021.100315 · Cited by 7
Le microbiote, un nouveau facteur de risque cardiovasculaire ?
Chong-Nguyen, C., Duboc, H., & Sokol, H. (2017) · La Presse Médicale · doi:10.1016/j.lpm.2017.06.005 · Cited by 8
Łukawska, A., & Mulak, A. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1394030 · Cited by 7
Xiao, P., Li, Q., Wang, L., Sun, G., Hou, H., Han, X., Feng, J. C., & Min, Y. (2025) · Poultry Science · doi:10.1016/j.psj.2025.105286 · Cited by 7
“An appropriate inflammatory state in the intestine may contribute to the maintenance of a healthy intestinal barrier function (Gadaleta et al., 2011; Feng et al., 2023c), as evidenced by increased mRNA expression levels of tight junction protein genes such as occludin, claudin-1 , and ZO-1 , along…”
Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review)
Muro, P., Jing, C., Qiao, Y., Wang, W., Wang, B., & Mao, F. (2025) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2025.5576 · Cited by 7
Gut microbiota and its metabolism in autism spectrum disorder: from pathogenesis to therapy
Bu, W., Chen, Z., Liu, B., & Jia, X. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1687691 · Cited by 10
Pleiotropic immunoregulation by bile acids in pathophysiology
Lin, B.-S., Yin, M., Xie, S.-A., Li, P., & Li, X. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1719092 · Cited by 8
Zhan, M., Zhao, C., Han, Y., Chen, B., Chen, Y., Song, M., Cao, Y., & Xiao, H. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c16340 · Cited by 7
Aljabban, J., Rohr, M., Borkowski, V. J., Nemer, M., Cohen, E., Hashi, N. J., Aljabban, H., Boateng, E., Syed, S. A., Mohammed, M., et al. (2022) · Journal of Pathology Informatics · doi:10.1016/j.jpi.2022.100094 · Cited by 7
“54 Targeting CCL20 has been proposed to target in-fl ammation and may be promising in treatment of IBD.”
BackgroundInfluentialLi, X.-H., Liu, L., & Wu, W. (2023) · Mediators of Inflammation · doi:10.1155/2023/4188510 · Cited by 8
“Scores ranged from 0 to 6 (1) few inflammatory cells with no epithelial degeneration; (2) mild inflammation with few signs of epithelial degeneration; (3) moderate inflammation with few epithelial ulcers; (4) moderate-tosevere inflammation with ulcers in 35%–50% of tissue sections; (5) moderate-to-severe inflammation…”
BackgroundImpact of intestinal microenvironments in obesity and bariatric surgery on shaping macrophages
Leyderman, M., Wilmore, J. R., Shope, T. R., Cooney, R. N., & Urao, N. (2023) · Immunometabolism · doi:10.1097/in9.0000000000000033 · Cited by 8
“In macrophages, signals from FXR downregulate several inflammatory cytokines, including IL-1 β , inducible isoforms of NO synthase (iNOS), TNF-α , IL-6, and cyclooxygenase (COX)-1 and COX-2 [117,118] , and thus promote M2-like polarization [115] .”
BackgroundAspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways
Lin, Q., Zhang, B., Dai, M., Cheng, Y., & Li, F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063424 · Cited by 9
“…intestine, FXR activation can impede the activation of inflammatory signaling pathways, foster the expression of intestinal tight junction proteins (claudin-1 and occludin), and minimize the permeability of the intestinal barrier, thus suppressing intestinal inflammation and barrier damage [20,21].”
BackgroundAmeliorative Effect of Glycyrrhizic Acid on Diosbulbin B-Induced Liver Injury and Its Mechanism
Wang, X., Shi, L.-L., Zhang, Y.-H., Zhu, H., Cao, S.-S., Shi, Y. Q., Shangguan, H., Liu, J.-P., & Xie, Y. (2025) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x25500120 · Cited by 7
The portal‐drained viscera release fibroblast growth factor 19 in humans
Koelfat, K. V. K., Bloemen, J. G., Jansen, P. L. M., Dejong, C. H. C., Schaap, F. G., & Damink, S. W. M. O. (2016) · Physiological Reports · doi:10.14814/phy2.13037 · Cited by 7
“Besides (postprandial) control of hepatic metabolism, bile salt/FXR signaling is implicated in other processes including gut barrier integrity and liver regeneration (Gadaleta et al. 2011; Zhang et al. 2012).”
BackgroundThe Mechanism of Important Components in Canine Fecal Microbiota Transplantation
Li, K., Yang, J., Zhou, X., Wang, H., Ren, Y., Huang, Y., Liu, H., Zhong, Z., Peng, G., Zheng, C., et al. (2022) · Veterinary Sciences · doi:10.3390/vetsci9120695 · Cited by 11
Yang, J., van Dijk, T. H., Koehorst, M., Havinga, R., de Boer, J. F., Kuipers, F., & van Zutphen, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044132 · Cited by 7
“Besides controlling metabolic pathways, the activation of FXR has been shown to improve the intestinal structure and integrity in several disease models [18,24,25].”
BackgroundResultThe Discovery of Obeticholic Acid ( Ocaliva™ ): First‐in‐Class FXR Agonist
Pellicciari, R., Pruzanski, M., & Gioiello, A. (2018) · Wiley eBooks · doi:10.1002/9783527808694.ch8 · Cited by 7
Jing, D., Liu, J., Qin, D., Lin, J., Li, T., Li, Y., & Duan, M. (2024) · Renal Failure · doi:10.1080/0886022x.2024.2368090 · Cited by 6
Wang, R., Feng, B., Yao, Q., Pan, Q., Yu, J., Liu, C., Wang, J., Li, L., Cao, H., & Xie, J. (2025) · Communications Biology · doi:10.1038/s42003-025-08261-y · Cited by 6
Gut Microbiota in Primary Sarcopenia: Mechanisms and Potential Therapeutic Targets
Chen, L., Chen, Y., Chen, W., Tan, H., Ye, L. P., Chen, J., & Xu, X. (2025) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl36204 · Cited by 7
Shi, Y., Lin, S. S., Shi, Y., & Xie, J. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s524111 · Cited by 6
“31 Bile acids also modulate inflammation indirectly by affecting inflammasome activity.”
Wang, M., Su, H., & Liu, J. (2025) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2025231 · Cited by 7
“FXR agonists, which are capable of regulating BA synthesis and inflammatory responses while improving in - testinal barrier function, are currently under therapeutic develop - ment for IBD and metabolic disorders [100,101].”
Bile acids and gut microbiota: interactions and impacts on polycystic ovary syndrome
Qian, H., Tao, J., Shi, L., Haiyan, S., Yang, L., Cui, L. J., Xu, W., & Wang, L. (2026) · Frontiers in Microbiomes · doi:10.3389/frmbi.2025.1702198 · Cited by 7
Guo, Y., Xu, X., Han, A., Song, F., Zhang, Y., Jiang, X., & Yu, W. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.157987 · Cited by 6
Katsigianni, S., & Koutsouraki, E. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05914-9 · Cited by 7
“…by taxa such as Lactobacillus , Clostridium cluster XIVα, Bifidobacterium , and Bacteroides generates metabolites (e.g., DCA, LCA, UDCA) that regulate host metabolism and inflammation via Farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5) signaling [53, 54, 137, 166, 167].”
Qu, F., Li, D., Zhang, S., Zhang, C., & Shen, A. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116396 · Cited by 6
Yin, G., Guo, Y., Ding, Q., Ma, S., Chen, F., Wang, Q., Chen, H., & Wang, H. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04068-9 · Cited by 6
“quasipneumoniae or Enterococcus faecium for 1 h and with 100 mM chenodeoxycholic acid (CDCA; Sigma, Germany) for 24 h [31, 32].”
MethodBariatric surgery attenuates colitis in an obese murine model
Li, S., Vinci, A., Behnsen, J., Cheng, C., Jellbauer, S., Raffatellu, M., Sousa, K. M., Edwards, R. A., Nguyen, N. T., Stamos, M. J., et al. (2016) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2016.10.024 · Cited by 6
“Furthermore, multiple evidences suggested that activation of FXR has beneficial effects on IBD in both animal models and humans [6,7].”
BackgroundXenobiotic and endobiotic handling by the mucosal immune system
Chen, M. L., & Sundrud, M. S. (2018) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000478 · Cited by 6
“Reduced FXR expression and function has been reported in mucosal biopsies from Crohn’s disease patients, and the small molecule FXR agonist, obeticholic acid (INT-747), is protective in mouse models of IBD [92,93].”
BackgroundInfluentialRashidbeygi, E., Rasaei, N., Amini, M. R., Salavatizadeh, M., Mohammadizadeh, M., & Hekmatdoost, A. (2025) · BMC Cardiovascular Disorders · doi:10.1186/s12872-025-04549-3 · Cited by 9
Jiang, Y. Z., Tang, Y., Liu, Z., Yang, X., Zhou, M.-Y., Liang, Y., Ding, J., & Liao, Y. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-02022-3 · Cited by 5
“For example, work by Gadaleta et al. has shown that intestinal FXR activation alleviates gut inflammation and reinforces intestinal barrier function (Gadaleta et al. 2011 ).”
Bile acids as gatekeepers: Orchestrating gut-liver axis for metabolic and immune balance
Chen, Q., Xin, L. I. U., & Jiang, Z.-H. (2026) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2026.01.001 · Cited by 6
Bile acid signaling, metabolism, and aging
Sun, J., Zhang, S., Jin, L., & Huang, W. (2026) · Liver Research · doi:10.1016/j.livres.2026.02.002 · Cited by 7
“56,57 During aging, FXR signaling responsiveness appears to be attenuated, contributing to the metabolic dysregulation and chronic low-grade inflammation that characterize the aging process.”
Németh, K., Tóth, I., Lányi, K., Schilling-Tóth, B. M., Csorba, S., Žaja, I. Ž., & Sterczer, Á. (2026) · Veterinary Sciences · doi:10.3390/vetsci13020182 · Cited by 7
Han, B., Wen, H., Li, Y., Wang, Y., Lv, X., Kang, M., Huang, W., Lan, Y., Tong, S., Zhang, M., et al. (2026) · The ISME Journal · doi:10.1093/ismejo/wrag028 · Cited by 7
“Other than that, the activation of FXR with synthetic agonists shielded mice from chemically caused intestinal inflammation by inhibiting pro-inflammatory cytokines synthesis and halting goblet cell degeneration [25].”
Gut microbial bile salt hydrolase as a metabolic gatekeeper in digestive homeostasis and disease
Chu, H., Song, X., Liu, C., Ma, T., & Cui, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1870619 · Cited by 7
Gut microbiota metabolites in inflammatory bowel disease: advances in mechanistic insights
Liang, Y., Zhou, Y., Luo, P., & Lin, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1827426 · Cited by 6
Xie, T., Cao, G.-Y., Zhang, S., Li, M., Jin, X., Liu, L., Wang, G., & Zhen, L. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01838 · Cited by 5
Yang, L., Zhou, X., Liu, J., Yang, G., Yu, J., Tan, W., Fang, X., Li, W., He, J., Ma, Q., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156584 · Cited by 5
Lactic acid bacteria in gut microbiota, probiotics and disease prevention
Aburjaile, F. F., de Jesus, L. C. L., da Silva, T. F., Drumond, M. M., Carvalho, R. D. D. O., Azevedo, V., & Mancha-Agresti, P. D. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-89875-1.00001-8 · Cited by 5
Viral Liver Disease and Intestinal Gut–Liver Axis
Kouroumalis, E., Tsomidis, I., & Voumvouraki, A. (2024) · Gastrointestinal Disorders · doi:10.3390/gidisord6010005 · Cited by 5
“FXR engagement can therefore preserve the epithelial barrier [158] and repair damage of the gut vascular barrier [159].”
BackgroundAdvancing care in primary biliary cholangitis: emerging insights and novel therapies
Vögelin, M., & Kremer, A. E. (2025) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2025.2516622 · Cited by 5
Laleman, W., Trebicka, J., & Verbeke, L. (2016) · Hepatology · doi:10.1002/hep.28771 · Cited by 5
“More specifically, reactivation of the FXR pathway was observed only in the ileum and not the jejunum of bile-duct– ligated rats, which paralleled selective functional restoration of intestinal integrity and coincided with a marked reduction in BT.”
BackgroundInfluentialGlycyrrhetic Acid Derivative TY501 Protects Against Lithocholic Acid–Induced Cholestasis
Zheng, X., Zhu, S., Zhou, Z., Liu, W., & Xu, W. (2017) · Drug Research · doi:10.1055/s-0043-122222 · Cited by 5
“FXR is a member of the nuclear hormone receptor superfamily, which plays an essential role in regulating bile acid, glucose, lipid homeostasis[6]and numerous hepatobiliary[7]and gastrointestinal diseases[8, 9].”
BackgroundTungland, B. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814649-1.00003-x · Cited by 5
Khan, A. H., Nolan, B., Stavniichuk, A., Merk, D., & Imig, J. D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1269261 · Cited by 5
Young, W., Jester, T., Stoll, M. L., & Ízcue, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-79026-8_19 · Cited by 5
Kong, D., Yu, S., Heegsma, J., Blokzijl, T., Qin, T., Pan, Y., Blokzijl, H., de Meijer, V. E., Duan, Y., Faber, K. N., et al. (2026) · Journal of nanobiotechnology · doi:10.1186/s12951-026-04477-0 · Cited by 4
“Beyond regulating lipid metabolism, FXR agonists are known to alleviate endoplasmic reticulum stress and suppress oxidative damage by upregulating antioxidant and anti-apoptotic pathways [42, 43].”
Lin, M., Huang, R., Li, W., Peng, H., Chen, J., Qiu, Y., Liu, Y., & Chen, L. (2025) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2025.110441 · Cited by 4
Curley, C. E., Lajczak, N., Adorini, L., Chonghaile, T. N., & Keely, S. J. (2025) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00086.2025 · Cited by 4
Self-citationBarnault, R., Inés, V.-N., Lotteau, V., Durantel, D., & Ramière, C. (2025) · Antiviral Research · doi:10.1016/j.antiviral.2025.106223 · Cited by 4
Gao, J., Li, L., Zhang, S., Zhao, H., Feng, B., Liu, C., Wang, X., Li, S., Li, Y., & Zhao, D. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.116056 · Cited by 4
Enteric nervous system in microbiota-associated gut inflammation
Yang, C., Lan, X., Zhong, H., Geng, J., & Wang, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1735727 · Cited by 4
Yue, S. R., Tan, Y. L., Gong, L., & Liao, F. (2026) · iScience · doi:10.1016/j.isci.2026.114961 · Cited by 5
Zhou, S., Li, Y., Qiu, X., Li, B., Hu, L., Tang, Z., Li, H., Li, S., Fang, Z., & Chen, H. (2024) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.13571 · Cited by 4
Physiological and pathophysiological role of endocrine fibroblast growth factors
Łukawska, A., & Mulak, A. (2022) · Postępy Higieny i Medycyny Doświadczalnej · doi:10.2478/ahem-2022-0045 · Cited by 4
Fan, A., Hou, B.-L., Tang, Z., Wang, T., Zhang, D.-B., Liang, Y.-N., & Wang, Z. (2023) · Journal of Medicinal Food · doi:10.1089/jmf.2023.k.0132 · Cited by 4
Petrášek, J., & Szabó, G. (2015) · Springer eBooks · doi:10.1007/978-3-319-20538-0_15 · Cited by 4
The Role of Bile Acid Receptors in Chronic Inflammatory Diseases
Park, R., & Ji, J. D. (2017) · Journal of Rheumatic Diseases · doi:10.4078/jrd.2017.24.5.253 · Cited by 4
“FXR-deficient mice exhibited more severe intestinal inflammation than wild type mice in studies that used colitis animal models such as dextran sodium sulfate (DSS)and trinitrobenzenesulfonic acid (TNBS)-induced colitis models, and FXR stimulation resulted in a decrease in pro-inflammatory cytokines production and che…”
BackgroundSteiner, C. A., & Higgins, P. (2018) · Springer eBooks · doi:10.1007/978-3-319-90578-5_23 · Cited by 4
Lai, H., Liu, X., Xin, S., Zheng, J., Liu, H., Ouyang, Y., Yang, H., Zeng, Y., Zou, Y., & Zeng, X. (2022) · BMC Medical Genomics · doi:10.1186/s12920-022-01240-w · Cited by 5
“In addition, NR1H4 dysfunctions may occur during the progression associated with inflammatory bowel disease, colorectal cancer in the gut [55, 56], fibrosis and hepatocellular carcinoma in the liver [57, 58].”
BackgroundNeumann, S., Peyroux, E. M., Woodall, M. J., Shields, N. J., Young, S. L., & Pattison, S. T. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88137 · Cited by 4
Ceulemans, L. J., Canovai, E., Verbeke, L., Pirenne, J., & Farré, R. (2016) · Acta chirurgica Belgica · doi:10.1080/00015458.2016.1215953 · Cited by 4
“[4,14,24,25,28] These cytokines are known to increase permeability in the intestinal epithelial monolayer by modulating epithelial and endothelial tight junction function,[29] as well as the actin cytoskeleton, leading to the disruption of the intestinal epithelial monolayer and intestinal hyperpermeability, which may…”
BackgroundInfluentialVito, F. D., Marasco, R., Suraci, E., Facciolo, A., Hribal, M. L., Sesti, G., Andreozzi, F., Luzza, F., & Fiorentino, T. V. (2025) · Diabetes · doi:10.2337/db25-0035 · Cited by 4
Spatiotemporal coordination between local flux and systemic homeostasis in the small intestine
Zhang, J., Zhang, S., Du, L., Zhao, Y., & Wang, D. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.07.009 · Cited by 3
Shang, K.-M., Elsheikha, H. M., Wei, Y.-J., Zhang, X.-X., Hou, X.-W., Yu, H., Cai, Y., Ni, H., Liu, R., Ma, H., et al. (2025) · Frontiers in Veterinary Science · doi:10.3389/fvets.2025.1669620 · Cited by 3
Kang, L., Feng, C., Tang, Z., Gu, W., Wang, Y., Pei, A., & Piao, M. (2026) · iScience · doi:10.1016/j.isci.2026.115275 · Cited by 3
Targeting the gut-lung axis in COPD: from microbial metabolites to fecal microbiota transplantation
Yu, Z., Qian, W., & Chu, Y. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1798150 · Cited by 5
“Concurrently, the restoration of secondary BA homeostasis may re-equilibrate FXR-TGR5 signaling cascades, thereby attenuating inflammatory signal amplification and mitigating pulmonary inflammatory damage (Guo et al., 2016; Gadaleta et al., 2011).”
Elhani, I., Bredon, M., Enea, D., Desmons, A., Arrivé, L., Bazille, C., Lefevre, A., Aouba, A., Bigot, A., de Moreuil, C., et al. (2026) · Pediatric Allergy and Immunology · doi:10.1111/pai.70343 · Cited by 3
From cirrhosis to hepatocellular carcinoma: An investigation into hepatitis C viral oncogenesis
Aljabban, J., Danis, N., Gurakar, M., Khorfan, K., Aljabban, N., Simsek, C., Salhi, H., Panahiazar, M., Hadley, D., Gurakar, A., et al. (2020) · Hepatology forum/Hepatology forum (Online) · doi:10.14744/hf.2019.0002 · Cited by 3
Bertolini, A., Bloks, V. W., Wilmink, M., Bos, E., van de Peppel, I. P., Eilers, R. E., Prins, S. D., Thomas, R., de Bruin, A., Verkade, H. J., et al. (2023) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2023.09.015 · Cited by 3
Wu, B.-Y., Xu, P., Cheng, L., Wang, Q., Qiu, H.-Y., Yan, X.-J., & Chen, S. (2024) · Clinical & Experimental Immunology · doi:10.1093/cei/uxae006 · Cited by 3
Dinerman, S., & Shu, Y. (2025) · International Journal of Translational Medicine · doi:10.3390/ijtm5010007 · Cited by 4
“Upon ligand binding, FXR translocates into the nucleus and heterodimerizes with RXR to induce the transcription of proteins such as small heterodimer protein (SHP) [153,154].”
Liu, T., Zhang, Y., Gao, F., Zhang, Z., Wang, M., Ma, C., Wang, Y., Ma, D., Wang, Z., Yan, X., et al. (2025) · Frontiers in Chemistry · doi:10.3389/fchem.2025.1551722 · Cited by 3
Reduced Cytokine Tumour Necrosis Factor by Pharmacological Intervention in a Preclinical Study
Mooranian, A., Chester, J., Johnston, E., Ionescu, C. M., Walker, D. P., Jones, M., Wagle, S. R., Kovačević, B., Foster, T., Mikov, M., et al. (2022) · Biomolecules · doi:10.3390/biom12070877 · Cited by 3
Bile Acids: A Bridge Linking Gut Microbiota and NAFLD
Zhang, J., Wang, C., Ji, X., Wu, F., Lin, Z., Zhou, Y., Xu, C., & Wang, F. (2022) · Advanced Gut & Microbiome Research · doi:10.1155/2022/4752148 · Cited by 3
“Another research has achieved a similar conclusion by using another FXR agonist OCA and proves that FXR downregulates the expression of key proinflammatory cytokines in colonic mucosa, suppressing IBD-related symptoms in mice, including mucous ulceration and hemorrhage [102].”
ResultSun, Y., Sun, K., Ling, H., & Xia, Q. (2025) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2025.5551 · Cited by 4
On the Pharmacology of Farnesoid X Receptor Agonists: Give me an "A", Like in "Acid"
Hambruch, E., Kinzel, O., & Kremoser, C. (2016) · Nuclear Receptor Research · doi:10.11131/2016/101207 · Cited by 3
Early Exposure to Gut Microbiome Reduces Hepatocellular Carcinoma Risks in Mice
Lee, Y.-M., Chang, W., Lei, F., Kor, C., Lai, H., Chen, Y., & Ma, W. (2020) · BioMed Research International · doi:10.1155/2020/9807379 · Cited by 3
FARNESOID X RECEPTOR AND REPRODUCTION
(2015) · Receptors & Clinical Investigation · doi:10.14800/rci.463 · Cited by 3
Role of Bile Acids and Nuclear Receptors in Acupuncture in Improving Crohn’s Disease
Shen, J., Qi, Q., Han, D., Liu, S., Huang, R., Zhu, Y., Zheng, H., Gu, K., Wu, H., & Liu, H. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/5814048 · Cited by 3
“[49] shows that the activation of FXR in the intestine lowered the expression of associated proinflammatory factors such as IL-6, MCP-1, and IL-1β and retain integrity of intestinal epithelial barrier function.”
BackgroundObeticholic acid: A new light in the shadows treating portal hypertension?
Gracia‐Sancho, J., Hernández–Gea, V., & García‐Pagán, J. C. (2014) · Hepatology · doi:10.1002/hep.27027 · Cited by 3
Metagenomic Analysis of Bile Salt Hydrolases in the Human Gut Microbiome
Jones, B. V., & Gahan, C. G. M. (2013) · Springer eBooks · doi:10.1007/978-1-4614-6418-1_777-1 · Cited by 3
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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