Therapeutic aspects of bile acid signalling in the gut‐liver axis

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials

(2021) Alessandro Mantovani et al.   Metabolites

The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a Rat NASH Model

(2021) Philipp Schwabl et al.   Biomedicines

FXR agonists for NASH: How are they different and what difference do they make?

(2021) Claus Kremoser   JOURNAL OF HEPATOLOGY

A nonbile acid farnesoid X receptor agonist tropifexor potently inhibits cholestatic liver injury and fibrosis by modulating the gut–liver axis

(2021) Yongtao Xiao et al.   LIVER INTERNATIONAL

Efficacy and safety of obeticholic acid in liver disease—A systematic review and meta-analysis

(2021) Anand V. Kulkarni et al.   Clinics and Research in Hepatology and Gastroenterology

Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy

(2020) John Y. L. Chiang et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Tropifexor, a highly potent FXR agonist, produces robust and dose-dependent reductions in hepatic fat and serum alanine aminotransferase in patients with fibrotic NASH after 12 weeks of therapy: FLIGHT-FXR Part C interim results

(2020) K.J. Lucas et al.   DIGESTIVE AND LIVER DISEASE

TGR5 promotes cholangiocarcinoma by interacting with mortalin

(2020) Ai-Di Li et al.   EXPERIMENTAL CELL RESEARCH

Cilofexor, a Nonsteroidal FXR Agonist, in Non‐Cirrhotic Patients with Nonalcoholic Steatohepatitis: A Phase 2 Randomized Controlled Trial

(2020) Keyur Patel et al.   HEPATOLOGY

Chronic Alcohol Consumption Increased Bile Acid Levels in Enterohepatic Circulation and Reduced Efficacy of Irinotecan

(2020) Xia Gong et al.   ALCOHOL AND ALCOHOLISM

Bile Acids Signal via TGR5 to Activate Intestinal Stem Cells and Epithelial Regeneration

(2020) Giovanni Sorrentino et al.   GASTROENTEROLOGY

A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis

(2020) Kris V. Kowdley et al.   JOURNAL OF HEPATOLOGY

Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside

(2020) James J. Beaudoin et al.   PHARMACOLOGY & THERAPEUTICS

Compound 18 Improves Glucose Tolerance in a Hepatocyte TGR5-dependent Manner in Mice

(2020) Marlena M. Holter et al.   Nutrients

Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans

(2020) Luca Maccioni et al.   Gut Microbes

Targeting the gut-liver-immune axis to treat cirrhosis

(2020) Thomas Henry Tranah et al.   GUT

Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality

(2020) Dalila COSTA et al.   JOURNAL OF HEPATOLOGY

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

(2020) Stefan Traussnigg et al.   WIENER KLINISCHE WOCHENSCHRIFT

TGR5 Signaling in Hepatic Metabolic Health

(2020) Marlena M. Holter et al.   Nutrients

Gut microbiome, liver immunology, and liver diseases

(2020) Rui Wang et al.   Cellular & Molecular Immunology

Targeting the four pillars of enterohepatic bile salt cycling; lessons from genetics and pharmacology

(2020) Roni F. Kunst et al.   HEPATOLOGY

Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH

(2020) Rohit Loomba et al.   HEPATOLOGY

Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression

(2020) Nisreen Nimer et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

(2020) Philip N. Newsome et al.   NEW ENGLAND JOURNAL OF MEDICINE

The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC

(2019) Michael Trauner et al.   HEPATOLOGY

NGM 282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients with Nonalcoholic Steatohepatitis

(2019) Stephen A. Harrison et al.   HEPATOLOGY

FGF19 Analogue as a Surgical Factor Mimetic that Contributes to Metabolic Effects Beyond Glucose Homeostasis

(2019) Alex M. DePaoli et al.   DIABETES

Gut microbiota in liver disease: Too much is harmful, nothing at all is not helpful either

(2019) Phillipp Hartmann et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis

(2019) Maren H. Harms et al.   JOURNAL OF HEPATOLOGY

Excellent safety and effectiveness of high dose myrcludex-b monotherapy administered for 48 weeks in hdv related compensated cirrhosis: a case report of three patients

(2019) Alessandro Loglio et al.   JOURNAL OF HEPATOLOGY

Obeticholic acid may increase the risk of gallstone formation in susceptible patients

(2019) Samer Al-Dury et al.   JOURNAL OF HEPATOLOGY

FxR-modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis

(2019) M. Sorribas et al.   JOURNAL OF HEPATOLOGY

Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study

(2019) Michael Trauner et al.   Lancet Gastroenterology & Hepatology

CONTROL: A randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients

(2019) Paul J. Pockros et al.   LIVER INTERNATIONAL

Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis

(2019) Christopher L. Bowlus et al.   Clinical Gastroenterology and Hepatology

Gut-liver axis signaling in portal hypertension

(2019) Benedikt Simbrunner et al.   WORLD JOURNAL OF GASTROENTEROLOGY

Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis

(2019) Mohammad Shadab Siddiqui et al.   JOURNAL OF HEPATOLOGY

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

(2019) Zobair M Younossi et al.   LANCET

Primary biliary cholangitis: pathogenesis and therapeutic opportunities

(2019) Aliya F. Gulamhusein et al.   Nature Reviews Gastroenterology & Hepatology

Organic solute transporter OSTα/β is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury

(2018) Melina M. Malinen et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression

(2018) O. Erice et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

An FXR Agonist Reduces Bile Acid Synthesis Independently of Increases in FGF19 in Healthy Volunteers

(2018) Amani Al-Khaifi et al.   GASTROENTEROLOGY

Na+ -taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice

(2018) Davor Slijepcevic et al.   HEPATOLOGY

A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis

(2018) Kris V. Kowdley et al.   HEPATOLOGY

Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice

(2018) Phillipp Hartmann et al.   HEPATOLOGY

Early assessment of safety and efficacy of tropifexor, a potent non bile-acid FXR agonist, in patients with primary biliary cholangitis: An interim analysis of an ongoing phase 2 study

(2018) C. Schramm et al.   JOURNAL OF HEPATOLOGY

Farnesoid X Receptor Agonists Obeticholic Acid and Chenodeoxycholic Acid Increase Bile Acid Efflux in Sandwich-Cultured Human Hepatocytes: Functional Evidence and Mechanisms

(2018) Cen Guo et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

(2018) Stephen A Harrison et al.   LANCET

Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis

(2018) Sangwon Byun et al.   Nature Communications

Animal models of portal hypertension

(2018) P. Königshofer et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

CYP7A1 expression in hepatocytes is retained with upregulated fibroblast growth factor 19 in pediatric biliary atresia

(2018) Yasuhiro Hasegawa et al.   HEPATOLOGY RESEARCH

Bile Acids Activated Receptors Regulate Innate Immunity

(2018) Stefano Fiorucci et al.   Frontiers in Immunology

Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1

(2018) Linbing Fan et al.   BIOLOGICAL CHEMISTRY

Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis

(2018) Richard Moreau et al.   GASTROENTEROLOGY

Intestinal immune dysregulation driven by dysbiosis promotes barrier disruption and bacterial translocation in rats with cirrhosis

(2018) Leticia Muñoz et al.   HEPATOLOGY

Ligand binding and heterodimerization with retinoid X receptor α (RXRα) induce farnesoid X receptor (FXR) conformational changes affecting coactivator binding

(2018) Na Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A multicenter, randomized, double-blind, placebo-controlled phase II trial

(2018) Gideon M. Hirschfield et al.   JOURNAL OF HEPATOLOGY

Hydrophilic bile acids prevent liver damage caused by lack of biliary phospholipid in Mdr2−/− mice

(2018) Renxue Wang et al.   JOURNAL OF LIPID RESEARCH

Pharmacological Applications of Bile Acids and Their Derivatives in the Treatment of Metabolic Syndrome

(2018) Maja Ðanić et al.   Frontiers in Pharmacology

Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice

(2017) Davor Slijepcevic et al.   HEPATOLOGY

Metabolic preconditioning protects BSEP / ABCB11 −/− mice against cholestatic liver injury

(2017) Claudia D. Fuchs et al.   JOURNAL OF HEPATOLOGY

Targeting the gut-liver axis in liver disease

(2017) Reiner Wiest et al.   JOURNAL OF HEPATOLOGY

The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction

(2017) Philipp Schwabl et al.   JOURNAL OF HEPATOLOGY

Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study

(2017) Vinod S Hegade et al.   LANCET

Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure

(2016) Joan Clària et al.   HEPATOLOGY

Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis

(2016) Anna Baghdasaryan et al.   JOURNAL OF HEPATOLOGY

Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study

(2016) Pavel Bogomolov et al.   JOURNAL OF HEPATOLOGY

Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats

(2016) María Úbeda et al.   JOURNAL OF HEPATOLOGY

Cholesterol 7α-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders

(2016) Jessica M. Ferrell et al.   JOURNAL OF LIPID RESEARCH

FXR Primes the Liver for Intestinal FGF15 Signaling by Transient Induction of β-Klotho

(2016) Ting Fu et al.   MOLECULAR ENDOCRINOLOGY

Immunology in the liver — from homeostasis to disease

(2016) Felix Heymann et al.   Nature Reviews Gastroenterology & Hepatology

A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis

(2016) Frederik Nevens et al.   NEW ENGLAND JOURNAL OF MEDICINE

FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis

(2016) Len Verbeke et al.   Scientific Reports

Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis

(2016) Malgorzata Milkiewicz et al.   Scientific Reports

The FXR Agonist Obeticholic Acid Prevents Gut Barrier Dysfunction and Bacterial Translocation in Cholestatic Rats

(2015) Len Verbeke et al.   AMERICAN JOURNAL OF PATHOLOGY

Efficacy of Obeticholic Acid in Patients With Primary Biliary Cirrhosis and Inadequate Response to Ursodeoxycholic Acid

(2015) Gideon M. Hirschfield et al.   GASTROENTEROLOGY

TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro

(2015) Maria Reich et al.   GUT

Pharmacological inhibition of apical sodium-dependent bile acid transporter changes bile composition and blocks progression of sclerosing cholangitis in multidrug resistance 2 knockout mice

(2015) Alexander G. Miethke et al.   HEPATOLOGY

The intrahepatic expression levels of bile acid transporters are inversely correlated with the histological progression of nonalcoholic fatty liver disease

(2015) Kazuya Okushin et al.   JOURNAL OF GASTROENTEROLOGY

Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments

(2015) Jaume Bosch et al.   JOURNAL OF HEPATOLOGY

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial

(2015) Brent A Neuschwander-Tetri et al.   LANCET

Novel therapeutic targets in primary biliary cirrhosis

(2015) Jessica K. Dyson et al.   Nature Reviews Gastroenterology & Hepatology

Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease

(2015) Ewa Wunsch et al.   Scientific Reports

The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid

(2014) J. R. F. Walters et al.   ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Cytoplasmic Tyrosine Phosphatase Shp2 Coordinates Hepatic Regulation of Bile Acid and FGF15/19 Signaling to Repress Bile Acid Synthesis

(2014) Shuangwei Li et al.   Cell Metabolism

The transrepressive activity of peroxisome proliferator-activated receptor alpha is necessary and sufficient to prevent liver fibrosis in mice

(2014) Michal Pawlak et al.   HEPATOLOGY

TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation

(2014) Alessia Perino et al.   JOURNAL OF CLINICAL INVESTIGATION

Bacterial infections in cirrhosis: A position statement based on the EASL Special Conference 2013

(2014) Rajiv Jalan et al.   JOURNAL OF HEPATOLOGY

Liver sinusoidal endothelial dysfunction after LPS administration: A role for inducible-nitric oxide synthase

(2014) Vincenzo La Mura et al.   JOURNAL OF HEPATOLOGY

Bile acids are nutrient signaling hormones

(2014) Huiping Zhou et al.   STEROIDS

Efficacy and Safety of the Farnesoid X Receptor Agonist Obeticholic Acid in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

(2013) Sunder Mudaliar et al.   GASTROENTEROLOGY

Hepatitis B and D Viruses Exploit Sodium Taurocholate Co-transporting Polypeptide for Species-Specific Entry into Hepatocytes

(2013) Yi Ni et al.   GASTROENTEROLOGY

Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats

(2013) Len Verbeke et al.   HEPATOLOGY

Bile acid receptors as targets for drug development

(2013) Frank G. Schaap et al.   Nature Reviews Gastroenterology & Hepatology

Nuclear receptor atlas of female mouse liver parenchymal, endothelial, and Kupffer cells

(2013) Zhaosha Li et al.   PHYSIOLOGICAL GENOMICS

Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice

(2012) Matthew J. Potthoff et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway

(2012) Senthilkumar Rajagopal et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice

(2012) Bo Kong et al.   HEPATOLOGY

Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes

(2011) Lihong Chen et al.   AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

Selective Activation of Nuclear Bile Acid Receptor FXR in the Intestine Protects Mice Against Cholestasis

(2011) Salvatore Modica et al.   GASTROENTEROLOGY

Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease

(2011) R. M. Gadaleta et al.   GUT

Intestinal bacterial translocation in rats with cirrhosis is related to compromised paneth cell antimicrobial host defense

(2011) Zora Teltschik et al.   HEPATOLOGY

Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut

(2011) Ekihiro Seki et al.   JOURNAL OF PHYSIOLOGY-LONDON

Bile salts and cholestasis

(2010) Lucas Maillette de Buy Wenniger et al.   DIGESTIVE AND LIVER DISEASE

Infections in Patients With Cirrhosis Increase Mortality Four-Fold and Should Be Used in Determining Prognosis

(2010) Vasiliki Arvaniti et al.   GASTROENTEROLOGY

Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system

(2010) D. P. Poole et al.   NEUROGASTROENTEROLOGY AND MOTILITY

Farnesoid X Receptor Critically Determines the Fibrotic Response in Mice but Is Expressed to a Low Extent in Human Hepatic Stellate Cells and Periductal Myofibroblasts

(2009) Peter Fickert et al.   AMERICAN JOURNAL OF PATHOLOGY

TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis

(2009) Charles Thomas et al.   Cell Metabolism

Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

(2009) Craig D. Fisher et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders

(2009) Verena Keitel et al.   HEPATOLOGY

Bile acids: regulation of synthesis

(2009) John Y. L. Chiang   JOURNAL OF LIPID RESEARCH

Bile-acid-induced cell injury and protection

(2009) Maria J Perez et al.   WORLD JOURNAL OF GASTROENTEROLOGY

β-Klotho and FGF-15/19 inhibit the apical sodium-dependent bile acid transporter in enterocytes and cholangiocytes

(2008) Jyoti Sinha et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Expression and function of the bile acid receptor TGR5 in Kupffer cells

(2008) Verena Keitel et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

(2008) A. F. Hofmann et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Farnesoid X Receptor Induces GLUT4 Expression Through FXR Response Element in the GLUT4 Promoter

(2008) Hong Shen et al.   CELLULAR PHYSIOLOGY AND BIOCHEMISTRY

Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7α-hydroxylase gene expression

(2008) Kwang-Hoon Song et al.   HEPATOLOGY

Targeting bile-acid signalling for metabolic diseases

(2008) Charles Thomas et al.   NATURE REVIEWS DRUG DISCOVERY