{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:03:13Z","timestamp":1792195393249,"version":"4.4.0"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Lithocholic acid (LCA) is a monohydroxy bile acid produced by intestinal flora, which has been found to be associated with a variety of hepatic and intestinal diseases. LCA is previously considered to be toxic, however, recent studies revealed that LCA and its derivatives may exert anti-inflammatory and anti-tumor effects under certain conditions. LCA goes through enterohepatic circulation along with other bile acids, here, we mainly discuss the effects of LCA on the gut-liver axis, including the regulation of gut microbiota, intestinal barrier, and relevant nuclear receptors (VDR, PXR) and G protein-coupled receptor five in related diseases. In addition, we also find that some natural ingredients are involved in regulating the detoxification and excretion of LCA, and the interaction with LCA also mediates its own biological activity.<\/jats:p>","DOI":"10.3389\/fphar.2022.910493","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T03:23:55Z","timestamp":1657164235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":63,"title":["The Effect of Lithocholic Acid on the Gut-Liver Axis"],"prefix":"10.3389","volume":"13","author":[{"given":"Wei","family":"Sheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"BSR20181011","DOI":"10.1042\/bsr20181011","article-title":"Preventive Effect of Artemisinin Extract against Cholestasis Induced via Lithocholic Acid Exposure","volume":"38","author":"Alkhedaide","year":"2018","journal-title":"Biosci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"63","DOI":"10.14715\/cmb\/2018.64.13.12","article-title":"Preventive Effect of Juniperus Procera Extract on Liver Injury Induced by Lithocholic Acid","volume":"64","author":"Alkhedaide","year":"2018","journal-title":"Cell Mol. Biol. (Noisy-le-grand)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"C447","DOI":"10.1152\/ajpcell.00416.2012","article-title":"Chenodeoxycholic Acid Stimulates Cl(-) Secretion via cAMP Signaling and Increases Cystic Fibrosis Transmembrane Conductance Regulator Phosphorylation in T84 Cells","volume":"305","author":"Ao","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"C1010","DOI":"10.1152\/ajpcell.00350.2015","article-title":"Lithocholic Acid Attenuates cAMP-dependent Cl- Secretion in Human Colonic Epithelial T84 Cells","volume":"310","author":"Ao","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/hep.28709","article-title":"Bile Acids and Nonalcoholic Fatty Liver Disease: Molecular Insights and Therapeutic Perspectives","volume":"65","author":"Arab","year":"2017","journal-title":"Hepatology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/s1388-1981(99)00031-1","article-title":"6alpha-hydroxylation of Taurochenodeoxycholic Acid and Lithocholic Acid by CYP3A4 in Human Liver Microsomes","volume":"1438","author":"Araya","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"B7","doi-asserted-by":"publisher","first-page":"16522","DOI":"10.3390\/ijms150916522","article-title":"Mechanisms Underlying the Anti-aging and Anti-tumor Effects of Lithocholic Bile Acid","volume":"15","author":"Arlia-Ciommo","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"34945","DOI":"10.18632\/oncotarget.26188","article-title":"Mechanisms through Which Lithocholic Acid Delays Yeast Chronological Aging under Caloric Restriction Conditions","volume":"9","author":"Arlia-Ciommo","year":"2018","journal-title":"Oncotarget"},{"key":"B9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1093\/emboj\/21.1.53","article-title":"CREB Activation Induced by Mitochondrial Dysfunction is a New Signaling Pathway that Impairs Cell Proliferation","volume":"21","author":"Arnould","year":"2002","journal-title":"EMBO J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1242\/jcs.013029","article-title":"Mechanisms Underlying P53 Regulation of PIK3CA Transcription in Ovarian Surface Epithelium and in Ovarian Cancer","volume":"121","author":"Astanehe","year":"2008","journal-title":"J. Cell Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1124\/jpet.119.256255","article-title":"Inhibition of Human Sulfotransferase 2A1-Catalyzed Sulfonation of Lithocholic Acid, Glycolithocholic Acid, and Taurolithocholic Acid by Selective Estrogen Receptor Modulators and Various Analogs and Metabolites","volume":"369","author":"Bansal","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.femsre.2004.09.003","article-title":"The Interaction between Bacteria and Bile","volume":"29","author":"Begley","year":"2005","journal-title":"FEMS Microbiol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e189","DOI":"10.1038\/oncsis.2015.49","article-title":"Lipid Metabolic Reprogramming in Cancer Cells","volume":"5","author":"Beloribi-Djefaflia","year":"2016","journal-title":"Oncogenesis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.mrrev.2004.08.001","article-title":"Bile Acids as Carcinogens in Human Gastrointestinal Cancers","volume":"589","author":"Bernstein","year":"2005","journal-title":"Mutat. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.4161\/cc.21754","article-title":"Lithocholic Acid Extends Longevity of Chronologically Aging Yeast Only if Added at Certain Critical Periods of Their Lifespan","volume":"11","author":"Burstein","year":"2012","journal-title":"Cell Cycle"},{"key":"B16","doi-asserted-by":"publisher","first-page":"112825","DOI":"10.1016\/j.biopha.2022.112825","article-title":"Jiangzhi Granule Attenuates Non-alcoholic Steatohepatitis through Modulating Bile Acid in Mice Fed High-Fat Vitamin D Deficiency Diet","volume":"149","author":"Cao","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B17","first-page":"1691","article-title":"Oral Administration of Oleanolic Acid, Isolated from Swertia Mussotii Franch, Attenuates Liver Injury, Inflammation, and Cholestasis in Bile Duct-Ligated Rats","volume":"8","author":"Chai","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/0003-9861(85)90559-4","article-title":"Purification and Characterization of Bile Salt Sulfotransferase from Human Liver","volume":"241","author":"Chen","year":"1985","journal-title":"Arch. Biochem. Biophys."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1097\/MIB.0000000000000499","article-title":"Antrum Mucosal Protein-18 Peptide Targets Tight Junctions to Protect and Heal Barrier Structure and Function in Models of Inflammatory Bowel Disease","volume":"21","author":"Chen","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"S96","DOI":"10.1016\/j.jfda.2018.02.004","article-title":"Effects of Processing Adjuvants on Traditional Chinese Herbs","volume":"26","author":"Chen","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"B21","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1194\/jlr.M044420","article-title":"Intestinal CYP3A4 Protects against Lithocholic Acid-Induced Hepatotoxicity in Intestine-specific VDR-Deficient Mice","volume":"55","author":"Cheng","year":"2014","journal-title":"J. Lipid Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1016\/j.cell.2015.11.004","article-title":"Gut Microbiota Orchestrates Energy Homeostasis during Cold","volume":"163","author":"Chevalier","year":"2015","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nature12820","article-title":"Diet Rapidly and Reproducibly Alters the Human Gut Microbiome","volume":"505","author":"David","year":"2014","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1194\/jlr.R054114","article-title":"Intestinal Transport and Metabolism of Bile Acids","volume":"56","author":"Dawson","year":"2015","journal-title":"J. Lipid Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1124\/dmd.107.017533","article-title":"Biotransformation of Lithocholic Acid by Rat Hepatic Microsomes: Metabolite Analysis by Liquid Chromatography\/mass Spectrometry","volume":"36","author":"Deo","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"B26","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1172\/JCI114257","article-title":"Cl- Secretion Induced by Bile Salts. A Study of the Mechanism of Action Based on a Cultured Colonic Epithelial Cell Line","volume":"84","author":"Dharmsathaphorn","year":"1989","journal-title":"J. Clin. Invest."},{"key":"B27","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.apsb.2015.01.004","article-title":"Bile Acid Nuclear Receptor FXR and Digestive System Diseases","volume":"5","author":"Ding","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/0006-2952(94)90156-2","article-title":"Phase I and Phase II Metabolism of Lithocholic Acid in Hepatic Acinar Zone 3 Necrosis. Evaluation in Rats by Combined Radiochromatography and Gas-Liquid Chromatography-Mass Spectrometry","volume":"48","author":"Dionne","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.steroids.2015.07.007","article-title":"Lithocholic Acid and Derivatives: Antibacterial Activity","volume":"104","author":"do Nascimento","year":"2015","journal-title":"Steroids"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1907271","article-title":"Completion of the Gut Microbial Epi-bile Acid Pathway","volume":"13","author":"Doden","year":"2021","journal-title":"Gut Microbes"},{"key":"B31","doi-asserted-by":"publisher","first-page":"105767","DOI":"10.1016\/j.phrs.2021.105767","article-title":"Dihydromyricetin Improves DSS-Induced Colitis in Mice via Modulation of Fecal-Bacteria-Related Bile Acid Metabolism","volume":"171","author":"Dong","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s11888-013-0203-4","article-title":"Lifestyle Modifications and Colorectal Cancer","volume":"10","author":"Durko","year":"2014","journal-title":"Curr. Colorectal Cancer Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.jcmgh.2021.12.001","article-title":"Bile Acid-Mediated Activation of Brown Fat Protects From Alcohol-Induced Steatosis and Liver Injury in Mice","volume":"13","author":"Fan","year":"2022","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.3389\/fimmu.2018.01853","article-title":"Bile Acids Activated Receptors Regulate Innate Immunity","volume":"9","author":"Fiorucci","year":"2018","journal-title":"Front. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41575-021-00566-7","article-title":"Role of Bile Acids and Their Receptors in Gastrointestinal and Hepatic Pathophysiology","author":"Fuchs","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/s0016-5085(76)80324-1","article-title":"Impaired Lithocholate Sulfation in the Rhesus Monkey: A Possible Mechanism for Chenodeoxycholate Toxicity","volume":"70","author":"Gadacz","year":"1976","journal-title":"Gastroenterology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1002\/mabi.201400475","article-title":"Galactosylated Poly(Ethyleneglycol)-Lithocholic Acid Selectively Kills Hepatoma Cells, While Sparing Normal Liver Cells","volume":"15","author":"Gankhuyag","year":"2015","journal-title":"Macromol. Biosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"393","DOI":"10.18632\/aging.100168","article-title":"Chemical Genetic Screen Identifies Lithocholic Acid as an Anti-Aging Compound that Extends Yeast Chronological Life Span in a TOR-Independent Manner, by Modulating Housekeeping Longevity Assurance Processes","volume":"2","author":"Goldberg","year":"2010","journal-title":"Aging (Albany NY)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3390\/microorganisms8040503","article-title":"Small Molecule Inhibitors of the Response Regulator ArsR Exhibit Bactericidal Activity against Helicobacter pylori","volume":"8","author":"Gonzalez","year":"2020","journal-title":"Microorganisms"},{"key":"B40","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1042\/0264-6021:3490189","article-title":"Lithocholic Acid and Sulphated Lithocholic Acid Differ in the Ability to Promote Matrix Metalloproteinase Secretion in the Human Colon Cancer Cell Line CaCo-2","volume":"349","author":"Halvorsen","year":"2000","journal-title":"Biochem. J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"G256","DOI":"10.1152\/ajpgi.00027.2007","article-title":"Human Cecal Bile Acids: Concentration and Spectrum","volume":"293","author":"Hamilton","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e0182467","DOI":"10.1371\/journal.pone.0182467","article-title":"In Vivo Therapeutic Effect of Combination Treatment with Metformin and Scutellaria Baicalensis on Maintaining Bile Acid Homeostasis","volume":"12","author":"Han","year":"2017","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.1021\/acs.molpharmaceut.8b00336","article-title":"Lithocholic Acid-Based Peptide Delivery System for an Enhanced Pharmacological and Pharmacokinetic Profile of Xenopus GLP-1 Analogs","volume":"15","author":"Han","year":"2018","journal-title":"Mol. Pharm."},{"key":"B44","doi-asserted-by":"publisher","first-page":"6558","DOI":"10.1039\/d1fo00671a","article-title":"Gut Microbiota Mediates the Effects of Curcumin on Enhancing Ucp1-Dependent Thermogenesis and Improving High-Fat Diet-Induced Obesity","volume":"12","author":"Han","year":"2021","journal-title":"Food Funct."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1124\/mol.65.5.1159","article-title":"Activators of the Rat Pregnane X Receptor Differentially Modulate Hepatic and Intestinal Gene Expression","volume":"65","author":"Hartley","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1016\/s0022-2275(20)34421-7","article-title":"Physicochemical Properties of Bile Acids and Their Relationship to Biological Properties: An Overview of the Problem","volume":"25","author":"Hofmann","year":"1984","journal-title":"J. Lipid Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1081\/dmr-200033475","article-title":"Detoxification of Lithocholic Acid, A Toxic Bile Acid: Relevance to Drug Hepatotoxicity","volume":"36","author":"Hofmann","year":"2004","journal-title":"Drug Metab. Rev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1002\/term.2506","article-title":"Intestinal Barrier Integrity and Inflammatory Bowel Disease: Stem Cell-Based Approaches to Regenerate the Barrier","volume":"12","author":"Holmberg","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"105444","DOI":"10.1016\/j.phrs.2021.105444","article-title":"Baicalin and the Liver-Gut System: Pharmacological Bases Explaining its Therapeutic Effects","volume":"165","author":"Hu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"184","DOI":"10.3109\/00498250903514607","article-title":"Kinetic Analysis of Bile Acid Sulfation by Stably Expressed Human Sulfotransferase 2A1 (SULT2A1)","volume":"40","author":"Huang","year":"2010","journal-title":"Xenobiotica"},{"key":"B51","doi-asserted-by":"publisher","first-page":"8558","DOI":"10.1096\/fj.201902618RR","article-title":"Capsaicin Improves Glucose Homeostasis by Enhancing Glucagon-Like Peptide-1 Secretion Through the Regulation of Bile Acid Metabolism via the Remodeling of the Gut Microbiota in Male Mice","volume":"34","author":"Hui","year":"","journal-title":"FASEB J."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1038\/s41366-020-0566-y","article-title":"Resveratrol Enhances Brown Adipose Tissue Activity and White Adipose Tissue Browning in Part by Regulating Bile Acid Metabolism via Gut Microbiota Remodeling","volume":"44","author":"Hui","year":"","journal-title":"Int. J. Obes. (Lond)"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.3390\/ijms19071975","article-title":"Lithocholic Acid is a Vitamin D Receptor Ligand That Acts Preferentially in the Ileum","volume":"19","author":"Ishizawa","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1002\/hep4.1778","article-title":"Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human-Like Bile Acid Composition","volume":"5","author":"Iwamoto","year":"2021","journal-title":"Hepatol. Commun."},{"key":"B55","doi-asserted-by":"publisher","first-page":"9435","DOI":"10.1074\/jbc.M209706200","article-title":"A G Protein-Coupled Receptor Responsive to Bile Acids","volume":"278","author":"Kawamata","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.3390\/jcm8081089","article-title":"Gut Microbiota and Risk of Persistent Nonalcoholic Fatty Liver Diseases","volume":"8","author":"Kim","year":"2019","journal-title":"J. Clin. Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"17838","DOI":"10.1074\/jbc.M210634200","article-title":"Protective Role of Hydroxysteroid Sulfotransferase in Lithocholic Acid-Induced Liver Toxicity","volume":"278","author":"Kitada","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e0168278","DOI":"10.1371\/journal.pone.0168278","article-title":"Evolutionary and Functional Diversification of the Vitamin D Receptor-Lithocholic Acid Partnership","volume":"11","author":"Kollitz","year":"2016","journal-title":"PLoS One"},{"key":"B59","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jsbmb.2011.07.011","article-title":"A Comparative Study of the Sulfation of Bile Acids and a Bile Alcohol by the Zebra Danio (Danio rerio) and Human Cytosolic Sulfotransferases (SULTs)","volume":"127","author":"Kurogi","year":"2011","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e14456","DOI":"10.14814\/phy2.14456","article-title":"The Secondary Bile Acids, Ursodeoxycholic Acid and Lithocholic Acid, Protect against Intestinal Inflammation by Inhibition of Epithelial Apoptosis","volume":"8","author":"Lajczak-McGinley","year":"2020","journal-title":"Physiol. Rep."},{"key":"B61","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/ni.2981","article-title":"The Kinase p38 Activated by the Metabolic Regulator AMPK and Scaffold TAB1 Drives the Senescence of Human T Cells","volume":"15","author":"Lanna","year":"2014","journal-title":"Nat. Immunol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1159\/000490836","article-title":"Farnesoid X Receptor (FXR) Interacts with Camp Response Element Binding Protein (CREB) to Modulate Glucagon-Like Peptide-1 (7-36) Amide (GLP-1) Secretion by Intestinal L Cell","volume":"47","author":"Li","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"B63","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.bbrc.2019.07.079","article-title":"A Novel Epigenetic Mechanism of FXR Inhibiting GLP-1 Secretion via miR-33 and its Downstream Targets","volume":"517","author":"Li","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B64","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/S1875-5364(20)30023-6","article-title":"Targeted Bile Acids and Gut Microbiome Profiles Reveal the Hepato-Protective Effect of WZ Tablet (Schisandra Sphenanthera Extract) against LCA-Induced Cholestasis","volume":"18","author":"Li","year":"2020","journal-title":"Chin. J. Nat. Med."},{"key":"B65","doi-asserted-by":"publisher","first-page":"530","DOI":"10.3390\/antiox11030530","article-title":"Piperine Attenuates Lithocholic Acid-Stimulated Interleukin-8 by Suppressing Src\/EGFR and Reactive Oxygen Species in Human Colorectal Cancer Cells","volume":"11","author":"Li","year":"2022","journal-title":"Antioxidants"},{"key":"B66","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s13402-017-0353-5","article-title":"Lithocholic Bile Acid Inhibits Lipogenesis and Induces Apoptosis in Breast Cancer Cells","volume":"41","author":"Luu","year":"2018","journal-title":"Cell Oncol. (Dordr)"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1126\/science.1070477","article-title":"Vitamin D receptor as an Intestinal Bile Acid Sensor","volume":"296","author":"Makishima","year":"2002","journal-title":"Science"},{"key":"B68","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1080\/19490976.2018.1549420","article-title":"In Vitro and In Vivo Characterization of Clostridium Scindens Bile Acid Transformations","volume":"10","author":"Marion","year":"2019","journal-title":"Gut Microbes"},{"key":"B69","first-page":"158","article-title":"Medical Chemical Laboratory Tests for the Practice","volume":"55","author":"Marki","year":"1966","journal-title":"Praxis"},{"key":"B70","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1124\/dmd.108.021501","article-title":"Role of Vitamin D Receptor in the Lithocholic Acid-Mediated CYP3A Induction In Vitro and In Vivo","volume":"36","author":"Matsubara","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1016\/j.bcp.2005.08.012","article-title":"Enhancement of Ligand-Dependent Vitamin D Receptor Transactivation by the Cardiotonic Steroid Bufalin","volume":"70","author":"Nakano","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1016\/j.cellsig.2008.06.014","article-title":"Bile Acids and Signal Transduction: Role in Glucose Homeostasis","volume":"20","author":"Nguyen","year":"2008","journal-title":"Cell Signal"},{"key":"B73","doi-asserted-by":"publisher","first-page":"10209","DOI":"10.3390\/ijms221910209","article-title":"Lithocholic Acid Induces miR21, Promoting PTEN Inhibition via STAT3 and ERK-1\/2 Signaling in Colorectal Cancer Cells","volume":"22","author":"Nguyen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3177\/jnsv.66.370","article-title":"Vitamin D Receptor Deletion Changes Bile Acid Composition in Mice Orally Administered Chenodeoxycholic Acid","volume":"66","author":"Nishida","year":"2020","journal-title":"J. Nutr. Sci. Vitaminol. (Tokyo)"},{"key":"B75","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1002\/jsfa.10834","article-title":"Prevention of the Rise in Plasma Cholesterol and Glucose Levels by Kaki-Tannin and Characterization of its Bile Acid Binding Capacity","volume":"101","author":"Nishida","year":"2021","journal-title":"J. Sci. Food Agric."},{"key":"B76","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.3390\/cells9102296","article-title":"PXR Functionally Interacts with NF-\u03baB and AP-1 to Downregulate the Inflammation-Induced Expression of Chemokine CXCL2 in Mice","volume":"9","author":"Okamura","year":"2020","journal-title":"Cells"},{"key":"B77","doi-asserted-by":"publisher","first-page":"6342","DOI":"10.1038\/ncomms7342","article-title":"Fat, Fibre and Cancer Risk in African Americans and Rural Africans","volume":"6","author":"O'Keefe","year":"2015","journal-title":"Nat. Commun."},{"key":"B78","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.tcb.2020.08.004","article-title":"Tight Junction Structure and Function Revisited","volume":"30","author":"Otani","year":"2020","journal-title":"Trends Cell Biol."},{"key":"B79","doi-asserted-by":"publisher","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":"B80","doi-asserted-by":"publisher","first-page":"153931","DOI":"10.1016\/j.phymed.2022.153931","article-title":"Frankincense Vinegar-Processing Improves the Absorption of Boswellic Acids by Regulating Bile Acid Metabolism","volume":"98","author":"Peng","year":"2022","journal-title":"Phytomedicine"},{"key":"B81","doi-asserted-by":"publisher","first-page":"e00176","DOI":"10.1128\/mSystems.00176-20","article-title":"Increasing the Hindgut Carbohydrate\/Protein Ratio by Cecal Infusion of Corn Starch or Casein Hydrolysate Drives Gut Microbiota-Related Bile Acid Metabolism To Stimulate Colonic Barrier Function","volume":"5","author":"Pi","year":"2020","journal-title":"mSystems"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e0176715","DOI":"10.1371\/journal.pone.0176715","article-title":"Lithocholic Acid Controls Adaptive Immune Responses by Inhibition of Th1 Activation Through the Vitamin D Receptor","volume":"12","author":"Pols","year":"2017","journal-title":"PLoS One"},{"key":"B83","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1194\/jlr.R500013-JLR200","article-title":"Bile Salt Biotransformations by Human Intestinal Bacteria","volume":"47","author":"Ridlon","year":"2006","journal-title":"J. Lipid Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1097\/MOG.0000000000000057","article-title":"Bile Acids and the Gut Microbiome","volume":"30","author":"Ridlon","year":"2014","journal-title":"Curr. Opin. Gastroenterol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1080\/19490976.2015.1127483","article-title":"Consequences of Bile Salt Biotransformations by Intestinal Bacteria","volume":"7","author":"Ridlon","year":"","journal-title":"Gut Microbes"},{"key":"B86","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1080\/19490976.2016.1150414","article-title":"Taurocholic Acid Metabolism by Gut Microbes and Colon Cancer","volume":"7","author":"Ridlon","year":"","journal-title":"Gut microbes"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1002\/cphy.c130018","article-title":"Hormonal Regulation of Hepatic Drug Biotransformation and Transport Systems","volume":"3","author":"Ruiz","year":"2013","journal-title":"Compr. Physiol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1097\/MIB.0000000000000204","article-title":"Intestinal Inflammation and Mucosal Barrier Function","volume":"20","author":"S\u00e1nchez de Medina","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"B89","doi-asserted-by":"publisher","first-page":"e13294","DOI":"10.14814\/phy2.13294","article-title":"The Yin and Yang of Bile Acid Action on Tight Junctions in a Model Colonic Epithelium","volume":"5","author":"Sarathy","year":"2017","journal-title":"Physiol. Rep."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1021\/jm7015864","article-title":"Novel Potent and Selective Bile Acid Derivatives as TGR5 Agonists: Biological Screening, Structure-Activity Relationships, and Molecular Modeling Studies","volume":"51","author":"Sato","year":"2008","journal-title":"J. Med. Chem."},{"key":"B91","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.chom.2020.01.021","article-title":"Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation","volume":"27","author":"Sinha","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B92","doi-asserted-by":"publisher","first-page":"5394","DOI":"10.1002\/anie.202015173","article-title":"Bile Acid Tethered Docetaxel-Based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes","volume":"60","author":"Sreekanth","year":"2021","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B93","doi-asserted-by":"publisher","first-page":"713149","DOI":"10.3389\/fphar.2021.713149","article-title":"(E)-7-Ethylidene-lithocholic Acid (7-ELCA) Is a Potent Dual Farnesoid X Receptor (FXR) Antagonist and GPBAR1 Agonist Inhibiting FXR-Induced Gene Expression in Hepatocytes and Stimulating Glucagon-like Peptide-1 Secretion From Enteroendocrine Cells","volume":"12","author":"Stefela","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"e25006","DOI":"10.1371\/journal.pone.0025006","article-title":"Bile Acid Metabolites in Serum: Intraindividual Variation and Associations with Coronary Heart Disease, Metabolic Syndrome and Diabetes Mellitus","volume":"6","author":"Steiner","year":"2011","journal-title":"PLoS One"},{"key":"B95","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1365-2362.1974.tb00373.x","article-title":"Bile Salt Sulphates in Cholestasis","volume":"4","author":"Stiehl","year":"1974","journal-title":"Eur. J. Clin. Invest."},{"key":"B96","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jsbmb.2008.01.003","article-title":"Lithocholic Acid Down-Regulation of NF-kappaB Activity Through Vitamin D Receptor in Colonic Cancer Cells","volume":"111","author":"Sun","year":"2008","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"31263","DOI":"10.1074\/jbc.M111.238147","article-title":"Interleukin-6 (IL-6) Regulates Claudin-2 Expression and Tight Junction Permeability in Intestinal Epithelium","volume":"286","author":"Suzuki","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B98","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.cmet.2009.08.001","article-title":"TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis","volume":"10","author":"Thomas","year":"2009","journal-title":"Cell Metab."},{"key":"B99","doi-asserted-by":"publisher","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":"B100","doi-asserted-by":"publisher","first-page":"e08883","DOI":"10.1016\/j.heliyon.2022.e08883","article-title":"The Effects of Sulfated Secondary Bile Acids on Intestinal Barrier Function and Immune Response in an Inflammatory in Vitro Human Intestinal Model","volume":"8","author":"van der Lugt","year":"2022","journal-title":"Heliyon"},{"key":"B101","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cbi.2012.08.023","article-title":"Pregnane X Receptor Mediated-Transcription Regulation Of CYP3A by Glycyrrhizin: A Possible Mechanism for its Hepatoprotective Property against Lithocholic Acid-Induced Injury","volume":"200","author":"Wang","year":"2012","journal-title":"Chem. Biol. Interact."},{"key":"B102","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1007\/s00726-014-1773-4","article-title":"Glutamine and Intestinal Barrier Function","volume":"47","author":"Wang","year":"2015","journal-title":"Amino Acids"},{"key":"B103","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s40168-019-0740-4","article-title":"Diet-induced Remission in Chronic Enteropathy is Associated with Altered Microbial Community Structure and Synthesis of Secondary Bile Acids","volume":"7","author":"Wang","year":"2019","journal-title":"Microbiome"},{"key":"B104","doi-asserted-by":"publisher","first-page":"G550","DOI":"10.1152\/ajpgi.00256.2016","article-title":"Ursodeoxycholic Acid and Lithocholic Acid Exert Anti-Inflammatory Actions in the Colon","volume":"312","author":"Ward","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B105","doi-asserted-by":"publisher","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":"B106","doi-asserted-by":"publisher","first-page":"7153","DOI":"10.3748\/wjg.v26.i45.7153","article-title":"Altered Metabolism of Bile Acids Correlates with Clinical Parameters and the Gut Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome","volume":"26","author":"Wei","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/s0168-8278(00)80183-x","article-title":"Isolation and Characterization of Cholic Acid 7alpha-Dehydroxylating Fecal Bacteria from Cholesterol Gallstone Patients","volume":"32","author":"Wells","year":"2000","journal-title":"J. Hepatol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"4230","DOI":"10.3748\/wjg.v13.i31.4230","article-title":"Lithocholic Acid Induction of the FGF19 Promoter in Intestinal Cells is Mediated by PXR","volume":"13","author":"Wistuba","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"786682","DOI":"10.3389\/fnut.2021.786682","article-title":"Grape Seed Proanthocyanidin Alleviates Intestinal Inflammation Through Gut Microbiota-Bile Acid Crosstalk in Mice","volume":"8","author":"Wu","year":"2021","journal-title":"Front. Nutr."},{"key":"B110","doi-asserted-by":"publisher","first-page":"3375","DOI":"10.1073\/pnas.051014398","article-title":"An Essential Role for Nuclear Receptors SXR\/PXR in Detoxification of Cholestatic Bile Acids","volume":"98","author":"Xie","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B111","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.apsb.2019.06.012","article-title":"PXR: A Center of Transcriptional Regulation in Cancer","volume":"10","author":"Xing","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"B112","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jep.2011.04.029","article-title":"Evaluation of Lysimachia Christinae Hance Extracts as Anticholecystitis and Cholagogic Agents in Animals","volume":"137","author":"Yang","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jnutbio.2017.10.003","article-title":"Cholesterol-lowering Effects of Dietary Pomegranate Extract and Inulin in Mice Fed an Obesogenic Diet","volume":"52","author":"Yang","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1007\/s00253-022-11813-5","article-title":"Targeting Intestinal Flora and its Metabolism to Explore the Laxative Effects of Rhubarb","volume":"106","author":"Yang","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.toxlet.2019.08.024","article-title":"The Protective Effect of Lithocholic Acid on the Intestinal Epithelial Barrier is Mediated by the Vitamin D Receptor via a SIRT1\/Nrf2 and NF-\u03baB Dependent Mechanism in Caco-2 Cells","volume":"316","author":"Yao","year":"2019","journal-title":"Toxicol. Lett."},{"key":"B116","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/imm.12045","article-title":"TGR5 Signalling Inhibits the Production of Pro-Inflammatory Cytokines by In Vitro Differentiated Inflammatory and Intestinal Macrophages in Crohn's Disease","volume":"139","author":"Yoneno","year":"2013","journal-title":"Immunology"},{"key":"B117","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/j.bmc.2015.01.048","article-title":"Stereoselective Synthesis, Biological Evaluation, and Modeling of Novel Bile Acid-derived G-Protein Coupled Bile Acid Receptor 1 (GP-BAR1, TGR5) Agonists","volume":"23","author":"Yu","year":"2015","journal-title":"Bioorg Med. Chem."},{"key":"B118","doi-asserted-by":"publisher","first-page":"698852","DOI":"10.3389\/fcimb.2021.698852","article-title":"Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease","volume":"11","author":"Yu","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.steroids.2014.04.016","article-title":"Bile Acids are Nutrient Signaling Hormones","volume":"86","author":"Zhou","year":"2014","journal-title":"Steroids"},{"key":"B120","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/s0022-2275(20)38317-6","article-title":"Detoxification of Lithocholic Acid. Elucidation of the Pathways of Oxidative Metabolism in Rat Liver Microsomes","volume":"30","author":"Zimniak","year":"1989","journal-title":"J. Lipid Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.910493\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T03:24:01Z","timestamp":1657164241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.910493\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,7]]},"references-count":120,"alternative-id":["10.3389\/fphar.2022.910493"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.910493","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,7]]},"article-number":"910493"}}