Bile Acids -- Contents -- Chapter 1 An Overview of Bile-Acid Synthesis, Chemistry and Function -- 1.1 The Bile Acids -- 1.2 Conjugated Bile-Acid Biosynthesis -- 1.3 Bile-Acid Regulation -- 1.3.1 Bile-Acid Receptors (FXR) -- 1.3.2 Cholesterol Receptors (LXR) (NR1H3) and (NR1H2) -- 1.4 Chemistry of Bile Acids and Their Effects on Digestion -- 1.5 Micelles -- 1.6 Biochemical Properties of Bile Acids and Their Effects on the GI Tract -- 1.6.1 Free Bile Acids -- 1.6.2 Glycine-Conjugated BAs -- 1.6.3 Taurine Conjugated dBAs -- 1.7 The Effect of pH on Bile-Acid Solubility -- 1.8 Potential Therapies for the Deleterious Effects of Bile Acids -- 1.9 Summary -- References -- Chapter 2 Bile-Acid Physiology and Measurement -- 2.1 Bile-Acid Physiology: The Enterohepatic Circulation -- 2.2 Transport in Blood -- 2.3 The Hepatocyte -- 2.4 Sodium Taurocholate Co-transporting Protein (NTCP) -- 2.5 Organic-Anion-Transporting Peptide (OATP) -- 2.6 Specificity of OATP and NTCP Transporters -- 2.7 Regulation of Expression -- 2.8 Transport across the Hepatocyte -- 2.9 Bile-Acid Export from the Hepatocyte -- 2.9.1 Bile-Salt Export Pump (BSEP) -- 2.9.2 Regulation of BSEP -- 2.9.3 Other Transporters that Export Bile Acid from the Hepatocyte -- 2.10 Bile Secretion -- 2.11 Water Secretion -- 2.12 Cholangiocytes -- 2.13 Cholangiocyte Secretion -- 2.14 Gallbladder -- 2.15 Small Bowel -- 2.16 Intestinal Fat Absorption -- 2.17 Bile-Acid Absorption -- 2.17.1 Apical Sodium-Dependent Bile-Acid Transporter (ASBT) -- 2.17.2 Regulation -- 2.17.3 Post-Translational Modification -- 2.18 Transport across the Enterocyte -- 2.19 Export into Portal Blood -- 2.20 Colon -- 2.20.1 Deconjugation -- 2.20.2 Oxidation of Hydroxyl Groups -- 2.20.3 Dehydroxylation -- 2.21 Measurement of Bile Acids -- 2.21.1 Extraction -- 2.21.2 Hydroxysteroid Dehydrogenases -- 2.21.3 Chromatographic Assays.

2.21.3.1 Gas-Liquid Chromatography (glc) -- 2.21.3.2 High-Performance Liquid Chromatography (hplc) -- 2.21.4 Radioimmunoassay -- Abbreviations -- References -- Chapter 3 Bile-Acid Induction of Apoptosis in Relation to Gastrointestinal Cancer -- 3.1 Introduction -- 3.2 Bile Acids Induce Oxidative/Nitrosative Stress in Cells of the GI Tract -- 3.3 Bile Acids Induce DNA Damage in Cells of the GI Tract -- 3.4 Bile Acids Activate NF-kB as a Stress Response and Survival Pathway Throughout the GI Tract -- 3.5 Bile Acids Increase Mutant Cells in the GI Tract -- 3.6 Repeated Exposure to High Concentrations of Bile Acids Probably Selects for Apoptosis Resistance in Cells of the GI Tract -- 3.7 Apoptosis Resistance and Increased Mutation -- 3.8 Modes of Cell Death: Apoptosis, Autophagy and Necrosis -- 3.9 Overview -- Acknowledgments -- References -- Chapter 4 The Genotoxicity of Bile Acids -- 4.1 Introduction -- 4.2 Definitions -- 4.3 Bile Acids as Carcinogens -- 4.4 DNA Adducts -- 4.5 Bile Acids cause DNA Damage -- 4.6 The Role of Reactive Oxygen and Nitrogen Species -- 4.7 Mutagenic Effects of Bile Acids -- 4.8 Bile Acids and Chromosomal Damage -- 4.9 Chemoprevention Strategies -- 4.10 Summary and Concluding Remarks -- References -- Chapter 5 Bile Acids and Colorectal Cancer -- 5.1 Introduction -- 5.2 Multi-stage Colorectal Carcinogenesis -- 5.3 Evidence that Bile Acids Play a Role in Colorectal Carcinogenesis -- 5.3.1 Activity of Bile Acids in Rodent Models of CRC -- 5.3.2 Human Observational Data -- 5.4 Mechanisms of the Carcinogenic Activity of Secondary Bile Acids -- 5.5 Colorectal Cancer Chemoprevention Strategies Targeting Bile Acids -- 5.5.1 Ursodeoxycholic Acid -- 5.5.2 Other Agents Targeting Mucosal Bile Acid Exposure -- 5.5.3 Therapeutic Anti-cancer Use of Bile Acid Conjugates -- 5.6 Summary -- Acknowledgement -- References.

Chapter 6 Bile Acids and Oesophageal Adenocarcinoma (OA) -- 6.1 Oesophageal Adenocarcinoma -- 6.2 Oesophageal Bile Acid Exposure -- 6.3 Bile Acids and Diet -- 6.4 Duodeno-Gastro-Oesophageal Reflux (DGOR) -- Animal Models -- 6.5 Duodeno-Gastro-Oesophageal Reflux (DGOR) -- Clinical Data -- 6.6 Measurement of Bile in the Oesophagus -- 6.7 Mechanisms behind the Carcinogenicity of Bile Acids -- 6.8 The Interplay between Acid and Bile in GORD -- 6.9 Deconjugation of Bile Acids in Nonacidic Stomach -- 6.10 Effect of Acidity on Bile Acid Solubility -- 6.11 Acid-Suppression Therapy and Risks of OA -- 6.12 Bile Acid Therapy -- 6.13 Conclusions -- Acknowledgements -- References -- Chapter 7 Bile Acids and Obesity -- 7.1 Obesity -- 7.1.1 Epidemiology -- 7.1.2 Morbidity and Mortality -- 7.2 Adipose Tissue -- 7.2.1 Regulation of Fatty Acid and Glucose Metabolism in Adipocytes -- 7.2.2 Adipose Tissue as an Endocrine Organ -- 7.3 Common Complications of Obesity -- 7.3.1 Insulin Resistance -- 7.3.2 Impaired Glucose Tolerance -- 7.3.3 Dyslipidemia -- 7.4 Effect of Bile Acids on Obesity -- 7.4.1 Bile Acids, the Farnesoid X Receptor (FXR) and Fat Metabolism -- 7.5 Bile-Acid Sequestrants -- 7.5.1 Chemical Composition of BAS -- 7.5.2 Effect of Bile-Acid Sequestrants on Type-2 Diabetes and Obesity -- 7.6 Summary -- References -- Chapter 8 The Role of Bile Acids in Cholesterol-Rich Gallstone Formation -- 8.1 Introduction -- 8.2 The Triple Defect of Cholesterol GBS Formation -- 8.3 Vesicles versus Micelles -- 8.4 Nucleation of Cholesterol Crystals -- 8.5 Promoters and Inhibitors of Nucleation -- 8.6 Stasis -- 8.7 Indirect Evidence that Gallbladder Motor Dysfunction/Stasis is Important in the Pathogenesis of GBS -- 8.8 The Octreotide Story -- 8.9 Biliary Phospholipid Fatty-Acid Composition -- 8.10 Biliary Bile-Acid Composition.

8.11 The Adverse Effects of Increased Proportions of DCA in Bile on Cholesterol Gallstone Formation -- 8.12 Mechanism for the Increase in the % Biliary DCA Conjugates in Bile during Octreotide Treatment -- 8.13 The Relationship between Colonic Transit and DCA Metabolism -- 8.14 The Role of Prolonged Intestinal Transit in the Pathogenesis of Conventional Cholesterol Gallstones -- 8.15 The Inter-Relationship between LBTT, Colonic Anaerobic Bacteriology, Bile-Acid-Metabolising Enzymes, Intraluminal pH and DCA Metabolism -- 8.16 Summary -- References -- Subject Index.