{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:07:40Z","timestamp":1777003660817,"version":"3.51.4"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T00:00:00Z","timestamp":1676678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heart Foundation","award":["CVON2018-27"],"award-info":[{"award-number":["CVON2018-27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bile acids facilitate the intestinal absorption of dietary lipids and act as signalling molecules in the maintenance of metabolic homeostasis. Farnesoid X receptor (FXR) is a bile acid-responsive nuclear receptor involved in bile acid metabolism, as well as lipid and glucose homeostasis. Several studies have suggested a role of FXR in the control of genes regulating intestinal glucose handling. We applied a novel dual-label glucose kinetic approach in intestine-specific FXR\u2212\/\u2212 mice (iFXR-KO) to directly assess the role of intestinal FXR in glucose absorption. Although iFXR-KO mice showed decreased duodenal expression of hexokinase 1 (Hk1) under obesogenic conditions, the assessment of glucose fluxes in these mice did not show a role for intestinal FXR in glucose absorption. FXR activation with the specific agonist GS3972 induced Hk1, yet the glucose absorption rate remained unaffected. FXR activation increased the duodenal villus length in mice treated with GS3972, while stem cell proliferation remained unaffected. Accordingly, iFXR-KO mice on either chow, short or long-term HFD feeding displayed a shorter villus length in the duodenum compared to wild-type mice. These findings indicate that delayed glucose absorption reported in whole-body FXR\u2212\/\u2212 mice is not due to the absence of intestinal FXR. Yet, intestinal FXR does have a role in the small intestinal surface area.<\/jats:p>","DOI":"10.3390\/ijms24044132","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T04:28:57Z","timestamp":1676867337000},"page":"4132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intestinal Farnesoid X Receptor Modulates Duodenal Surface Area but Does Not Control Glucose Absorption in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Jiufang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo H.","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn","family":"Koehorst","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick","family":"Havinga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6759-3291","authenticated-orcid":false,"given":"Jan Freark","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2518-737X","authenticated-orcid":false,"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"},{"name":"Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"},{"name":"European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"van Zutphen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands"},{"name":"Faculty Campus Frysl\u00e2n, University of Groningen, 8911CE Leeuwarden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nrendo.2014.60","article-title":"Beyond intestinal soap\u2014Bile acids in metabolic control","volume":"10","author":"Kuipers","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"416","DOI":"10.7326\/0003-4819-121-6-199409150-00004","article-title":"Cholestyramine Therapy for Dyslipidemia in Non\u2013Insulin-dependent Diabetes Mellitus: A Short-Term, Double-Blind, Crossover Trial","volume":"121","author":"Garg","year":"1994","journal-title":"Ann. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.jdiacomp.2017.01.011","article-title":"Bile acid sequestrants for glycemic control in patients with type 2 diabetes: A systematic review with meta-analysis of randomized controlled trials","volume":"31","author":"Hansen","year":"2017","journal-title":"J. Diabetes Complicat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/dom.13080","article-title":"The bile acid-sequestering resin sevelamer eliminates the acuteGLP-1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes","volume":"20","author":"Rohde","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.2337\/db11-0030","article-title":"Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity","volume":"60","author":"Prawitt","year":"2011","journal-title":"Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1053\/j.gastro.2017.01.055","article-title":"Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease","volume":"152","author":"Tailleux","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1111\/liv.14209","article-title":"CONTROL: A randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients","volume":"39","author":"Pockros","year":"2019","journal-title":"Liver Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/hep.31205","article-title":"Cilofexor, a Nonsteroidal FXR Agonist, in Patients with Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial","volume":"72","author":"Patel","year":"2020","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00508-020-01735-5","article-title":"Open-label phase II study evaluating safety and efficacy of the non-steroidal farnesoid X receptor agonist PX-104 in non-alcoholic fatty liver disease","volume":"133","author":"Traussnigg","year":"2021","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1053\/j.gastro.2013.05.042","article-title":"Efficacy and Safety of the Farnesoid X Receptor Agonist Obeticholic Acid in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease","volume":"145","author":"Mudaliar","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nature13135","article-title":"FXR is a molecular target for the effects of vertical sleeve gastrectomy","volume":"509","author":"Ryan","year":"2014","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2019388118","DOI":"10.1073\/pnas.2019388118","article-title":"Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice","volume":"118","author":"Ding","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s11605-018-3938-z","article-title":"Concomitant PPAR\u03b1 and FXR Activation as a Putative Mechanism of NASH Improvement after Gastric Bypass Surgery: A GEO Datasets Analysis","volume":"23","author":"Mazzini","year":"2019","journal-title":"J. Gastrointest. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nm.3760","article-title":"Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance","volume":"21","author":"Fang","year":"2015","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature04330","article-title":"Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation","volume":"439","author":"Watanabe","year":"2006","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11039","DOI":"10.1074\/jbc.M510258200","article-title":"The Farnesoid X Receptor Modulates Adiposity and Peripheral Insulin Sensitivity in Mice","volume":"281","author":"Cariou","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1084\/jem.20171965","article-title":"Bile acids in glucose metabolism in health and disease","volume":"215","author":"Shapiro","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1073\/pnas.0509592103","article-title":"Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor","volume":"103","author":"Inagaki","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1053\/j.gastro.2016.12.037","article-title":"Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice","volume":"152","author":"Schonewille","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1002\/hep.29857","article-title":"Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism","volume":"68","author":"Pathak","year":"2018","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1038\/ncomms3384","article-title":"Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity","volume":"4","author":"Li","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1038\/ncomms10166","article-title":"Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction","volume":"6","author":"Jiang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7629","DOI":"10.1038\/ncomms8629","article-title":"Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells","volume":"6","author":"Trabelsi","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ceulemans, L.J., Verbeke, L., Decuypere, J.-P., Farr\u00e9, R., De Hertogh, G., Lenaerts, K., Jochmans, I., Monbaliu, D., Nevens, F., and Tack, J. (2017). Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169331"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1136\/gut.2010.212159","article-title":"Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease","volume":"60","author":"Gadaleta","year":"2011","journal-title":"Gut"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1128\/MCB.25.1.78-87.2005","article-title":"Mice without the Regulator Gene Rsc1A1 Exhibit Increased Na +-d-Glucose Cotransport in Small Intestine and Develop Obesity","volume":"25","author":"Osswald","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1210\/jc.2014-3144","article-title":"Accelerated Intestinal Glucose Absorption in Morbidly Obese Humans: Relationship to Glucose Transporters, Incretin Hormones, and Glycemia","volume":"100","author":"Nguyen","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.cmet.2016.01.018","article-title":"Bile Diversion in Roux-en-Y Gastric Bypass Modulates Sodium-Dependent Glucose Intestinal Uptake","volume":"23","author":"Baud","year":"2016","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10315","DOI":"10.1074\/jbc.M807317200","article-title":"An Increased Flux through the Glucose 6-Phosphate Pool in Enterocytes Delays Glucose Absorption in Fxr\u2013\/\u2013 Mice","volume":"284","author":"Grefhorst","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1194\/jlr.M700330-JLR200","article-title":"Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine","volume":"48","author":"Kim","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Stott, N.L., and Marino, J.S. (2020). High Fat Rodent Models of Type 2 Diabetes: From Rodent to Human. Nutrients, 12.","DOI":"10.3390\/nu12123650"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1172\/JCI76738","article-title":"Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease","volume":"125","author":"Jiang","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1007\/s00125-013-2913-1","article-title":"Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding","volume":"56","author":"Turner","year":"2013","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.jhep.2019.08.005","article-title":"Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development","volume":"71","author":"Mouries","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114430","DOI":"10.1016\/j.bcp.2021.114430","article-title":"Intestine-specific FXR agonists as potential therapeutic agents for colorectal cancer","volume":"186","author":"Yin","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1038\/s41374-020-0439-y","article-title":"Enhanced alcoholic liver disease in mice with intestine-specific farnesoid X receptor deficiency","volume":"100","author":"Huang","year":"2020","journal-title":"Lab. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.3389\/fimmu.2018.01270","article-title":"Cytokine Tuning of Intestinal Epithelial Function","volume":"9","author":"Andrews","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.bbadis.2011.04.005","article-title":"Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-\u03baB signaling in the intestine","volume":"1812","author":"Gadaleta","year":"2011","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1586\/17474124.2014.887439","article-title":"Glucose absorption in small intestinal diseases","volume":"8","author":"Thazhath","year":"2014","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"41930","DOI":"10.1074\/jbc.M306309200","article-title":"Enterohepatic Circulation of Bile Salts in Farnesoid X Receptor-deficient Mice: Efficient Intestinal Bile Salt Absorption in the Absence of Ileal Bile Acid-Binding Protein","volume":"278","author":"Kok","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1172\/JCI21025","article-title":"Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c","volume":"113","author":"Watanabe","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0092-8674(00)00062-3","article-title":"Targeted Disruption of the Nuclear Receptor FXR\/BAR Impairs Bile Acid and Lipid Homeostasis","volume":"102","author":"Sinal","year":"2000","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100344","DOI":"10.1016\/j.jhepr.2021.100344","article-title":"Ablation of liver Fxr results in an increased colonic mucus barrier in mice","volume":"3","author":"Ijssennagger","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12848","DOI":"10.1111\/jcmm.15881","article-title":"A novel role for farnesoid X receptor in the bile acid-mediated intestinal glucose homeostasis","volume":"24","author":"Zhao","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1085\/jgp.50.5.1173","article-title":"Small Intestinal Glucose Transport: Proximal-Distal Kinetic Gradients","volume":"50","author":"Rider","year":"1967","journal-title":"J. Gen. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev.nutr.28.061807.155518","article-title":"Sugar Absorption in the Intestine: The Role of GLUT2","volume":"28","author":"Kellett","year":"2008","journal-title":"Annu. Rev. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11330","DOI":"10.1073\/pnas.211357698","article-title":"Normal kinetics of intestinal glucose absorption in the absence of GLUT2: Evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum","volume":"98","author":"Burcelin","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1053\/gast.2003.50009","article-title":"Intestinal glucose transport: Evidence for a membrane traffic\u2013based pathway in humans","volume":"124","author":"Santer","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s102380200018","article-title":"A simple new method to calculate small intestine absorptive surface in the rat","volume":"2","author":"Kisielinski","year":"2002","journal-title":"Clin. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3382\/japr.2006-00116","article-title":"Effect of Formic Acid and Plant Extracts on Growth, Nutrient Digestibility, Intestine Mucosa Morphology, and Meat Yield of Broilers","volume":"16","author":"Hernandez","year":"2007","journal-title":"J. Appl. Poult. Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Soares, A., Beraldi, E.J., Ferreira, P.E.B., Bazotte, R.B., and Buttow, N.C. (2015). Intestinal and neuronal myenteric adaptations in the small intestine induced by a high-fat diet in mice. BMC Gastroenterol., 15.","DOI":"10.1186\/s12876-015-0228-z"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1177\/1535370218777762","article-title":"Obesity, independent of diet, drives lasting effects on intestinal epithelial stem cell proliferation in mice","volume":"243","author":"Zhou","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1258\/la.2009.009112","article-title":"Surface area assessment of the murine intestinal tract as a prerequisite for oral dose translation from mouse to man","volume":"44","author":"Casteleyn","year":"2010","journal-title":"Lab. Anim."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.apsb.2015.01.001","article-title":"Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids","volume":"5","author":"Ferrebee","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ajpath.2014.10.009","article-title":"The FXR Agonist Obeticholic Acid Prevents Gut Barrier Dysfunction and Bacterial Translocation in Cholestatic Rats","volume":"185","author":"Verbeke","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1155\/2012\/538452","article-title":"The Impact of Farnesoid X Receptor Activation on Intestinal Permeability in Inflammatory Bowel Disease","volume":"26","author":"Stojancevic","year":"2012","journal-title":"Can. J. Gastroenterol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"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., and Verspaget, H.W. (2011). Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023745"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.acthis.2007.08.001","article-title":"Immunolocalization of farnesoid X receptor (FXR) in mouse tissues using tissue microarray","volume":"110","author":"Higashiyama","year":"2008","journal-title":"Acta Histochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41575-020-00357-6","article-title":"Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium","volume":"18","author":"Heppert","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00427-012-0422-8","article-title":"Stem cells and lineages of the intestine: A developmental and evolutionary perspective","volume":"223","author":"Takashima","year":"2013","journal-title":"Dev. Genes Evol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7103","DOI":"10.1096\/fj.201903244R","article-title":"Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR-PI3K\/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria","volume":"34","author":"Song","year":"2020","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"G81","DOI":"10.1152\/ajpgi.00065.2015","article-title":"Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling","volume":"310","author":"Dossa","year":"2016","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1124\/jpet.108.145409","article-title":"Farnesoid X Receptor Deficiency in Mice Leads to Increased Intestinal Epithelial Cell Proliferation and Tumor Development","volume":"328","author":"Maran","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1042\/BJ20102096","article-title":"Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage","volume":"438","author":"Lian","year":"2011","journal-title":"Biochem. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1016\/j.cellsig.2013.08.035","article-title":"Hexokinase 1 blocks apoptotic signals at the mitochondria","volume":"25","author":"Schindler","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.cellsig.2010.04.010","article-title":"A functional RNAi screen identifies hexokinase 1 as a modifier of type II apoptosis","volume":"22","author":"Schindler","year":"2010","journal-title":"Cell. Signal."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12967-017-1175-y","article-title":"Influence of diet on the gut microbiome and implications for human health","volume":"15","author":"Singh","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jnutbio.2019.03.017","article-title":"The role of diet and intestinal microbiota in the development of metabolic syndrome","volume":"70","author":"Camargo","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"33275","DOI":"10.1074\/jbc.M204935200","article-title":"cis Elements of the Villin Gene Control Expression in Restricted Domains of the Vertical (Crypt) and Horizontal (Duodenum, Cecum) Axes of the Intestine","volume":"277","author":"Madison","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1177\/0023677212473714","article-title":"A Novel Approach to Monitor Glucose Metabolism Using Stable Isotopically Labelled Glucose in Longitudinal Studies in Mice","volume":"47","author":"Laskewitz","year":"2013","journal-title":"Lab. Anim."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/BF01070942","article-title":"Application of the Wagner-Nelson absorption method to the two-compartment open model","volume":"2","author":"Wagner","year":"1974","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41575-018-0081-y","article-title":"Tales from the crypt: New insights into intestinal stem cells","volume":"16","author":"Gehart","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"G283","DOI":"10.1152\/ajpgi.00462.2010","article-title":"Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model","volume":"300","author":"Fijlstra","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"da Silva Ferreira, A.R., Wardill, H.R., Havinga, R., Tissing, W., and Harmsen, H.J. (2021). Prophylactic Treatment with Vitamins C and B2 for Methotrexate-Induced Gastrointestinal Mucositis. Biomolecules, 11.","DOI":"10.3390\/biom11010034"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1194\/jlr.RA119000243","article-title":"A Human-like Bile Acid Pool Induced by Deletion of Hepatic Cyp2c70 Modulates Effects of FXR Activation in Mice","volume":"61","author":"Verkade","year":"2020","journal-title":"J. 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