Korean J Gastroenterol.  2024 Apr;83(4):133-142. 10.4166/kjg.2023.119.

Bile Acid Diarrhea

• Kim HJ
• Kim HJ

• KMID: 2555646
• DOI: http://doi.org/10.4166/kjg.2023.119

Abstract

Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD patients, a portion of bile from the small intestine that is normally controlled by enterohepatic circulation is present at a high concentration in the lumen of the large intestine, resulting in increased motility and secretion of the large intestine. The prevalence of BAD is estimated to be 1–2% of the general population, and it comprises one-third of the instances of diarrhea-predominant irritable bowel syndrome. The clinical symptoms of BAD include chronic diarrhea, increased frequency of defecation, urgency to defecate, fecal incontinence, and cramping abdominal pain. The pathophysiology of BAD has not yet been fully elucidated. However, recent studies have reported increased intestinal permeability, shortened intestinal transit time, and changes in the intestinal microbial community to be the possible causes of BAD. Although fecal and serum bile acid tests are widely used for diagnosis, new test methods that are non-invasive, inexpensive, and have high sensitivity and specificity are needed at various institutions to facilitate the diagnosis. The selenium homo-tauro-cholic acid (SeHCAT) test is the gold standard for BAD diagnosis and severity assessment. The validation of several other serum markers, such as 7-hydroxy-4-cholesten-3-one (serum 7αC4) and the fibroblast growth factor 19 (FGF19) for use in clinical practice is ongoing. Although bile acid sequestrants are the mainstay of treatment, the development of drugs that are more effective and have better compliance is required. Farnesoid X receptor (FXR) agonists are showing promising results.

Keyword

Bile acids and salts; Diarrhea, chronic; Physiopathology; Diagnosis; Treatment; 23-seleno-25-homotaurocholic acid (SeHCAT)

Reference

1. Marin JJ, Macias RI, Briz O, Banales JM, Monte MJ. 2015; Bile acids in physiology, pathology and pharmacology. Curr Drug Metab. 17:4–29. DOI: 10.2174/1389200216666151103115454. PMID: 26526836.

2. Brunner H, Northfield TC, Hofmann AF, Go VL, Summerskill WH. 1974; Gastric emptying and secretion of bile acids, cholesterol, and pancreatic enzymes during digestion. Duodenal perfusion studies in healthy subjects. Mayo Clin Proc. 49:851–860.

3. Walters JR. 2010; Defining primary bile acid diarrhea: making the diagnosis and recognizing the disorder. Expert Rev Gastroenterol Hepatol. 4:561–567. DOI: 10.1586/egh.10.54. PMID: 20932141.

4. Vijayvargiya P, Camilleri M. 2019; Current practice in the diagnosis of bile acid diarrhea. Gastroenterology. 156:1233–1238. DOI: 10.1053/j.gastro.2018.11.069. PMID: 30844373.

5. Fromm H, Malavolti M. 1986; Bile acid-induced diarrhoea. Clin Gastroenterol. 15:567–582. DOI: 10.1016/S0300-5089(21)00739-2. PMID: 3742841.

6. Hofmann AF, Mangelsdorf DJ, Kliewer SA. 2009; Chronic diarrhea due to excessive bile acid synthesis and not defective ileal transport: a new syndrome of defective fibroblast growth factor 19 release. Clin Gastroenterol Hepatol. 7:1151–1154. DOI: 10.1016/j.cgh.2009.07.026. PMID: 19665580. PMCID: PMC2850200.

7. Chiang JY. 2009; Bile acids: regulation of synthesis. J Lipid Res. 50:1955–1966. DOI: 10.1194/jlr.R900010-JLR200. PMID: 19346330. PMCID: PMC2739756.

8. Bunnett NW. 2014; Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract. J Physiol. 592:2943–2950. DOI: 10.1113/jphysiol.2014.271155. PMID: 24614746. PMCID: PMC4214650.

9. Walters JR, Tasleem AM, Omer OS, Brydon WG, Dew T, le Roux CW. 2009; A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol. 7:1189–1194. DOI: 10.1016/j.cgh.2009.04.024. PMID: 19426836.

10. Wingate DL, Krag E, Mekhjian HS, Phillips SF. 1973; Relationships between ion and water movement in the human jejunum, ileum and colon during perfusion with bile acids. Clin Sci Mol Med. 45:593–606. DOI: 10.1042/cs0450593. PMID: 4759510.

11. Kirwan WO, Smith AN, Mitchell WD, Falconer JD, Eastwood MA. 1975; Bile acids and colonic motility in the rabbit and the human. Gut. 16:894–902. DOI: 10.1136/gut.16.11.894. PMID: 1193418. PMCID: PMC1413128.

12. Bampton PA, Dinning PG, Kennedy ML, Lubowski DZ, Cook IJ. 2002; The proximal colonic motor response to rectal mechanical and chemical stimulation. Am J Physiol Gastrointest Liver Physiol. 282:G443–G449. DOI: 10.1152/ajpgi.00194.2001. PMID: 11841994.

13. Scarpello JH, Hodgson E, Howlett HC. 1998; Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. Diabet Med. 15:651–656. DOI: 10.1002/(SICI)1096-9136(199808)15:8<651::AID-DIA628>3.0.CO;2-A.

14. Pattni S, Walters JR. 2009; Recent advances in the understanding of bile acid malabsorption. Br Med Bull. 92:79–93. DOI: 10.1093/bmb/ldp032. PMID: 19900947.

15. Johnston IM, Nolan JD, Pattni SS, et al. 2016; Characterizing factors associated with differences in FGF19 blood levels and synthesis in patients with primary bile acid diarrhea. Am J Gastroenterol. 111:423–432. DOI: 10.1038/ajg.2015.424. PMID: 26856750.

16. Chang C, Jiang J, Sun R, Wang S, Chen H. 2022; Downregulation of serum and distal ileum fibroblast growth factor19 in bile acid diarrhoea patients. Dig Dis Sci. 67:872–879. DOI: 10.1007/s10620-021-07042-x. PMID: 34041651.

17. Montagnani M, Love MW, Rössel P, Dawson PA, Qvist P. 2001; Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption. Scand J Gastroenterol. 36:1077–1080. DOI: 10.1080/003655201750422693. PMID: 11589382.

18. Oelkers P, Kirby LC, Heubi JE, Dawson PA. 1997; Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J Clin Invest. 99:1880–1887. DOI: 10.1172/JCI119355. PMID: 9109432. PMCID: PMC508012.

19. Ho RH, Leake BF, Urquhart BL, Gregor JC, Dawson PA, Kim RB. 2011; Functional characterization of genetic variants in the apical sodium-dependent bile acid transporter (ASBT; SLC10A2). J Gastroenterol Hepatol. 26:1740–1748. DOI: 10.1111/j.1440-1746.2011.06805.x. PMID: 21649730. PMCID: PMC3170668.

20. Camilleri M. 2014; Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms. J Physiol. 592:2967–2980. DOI: 10.1113/jphysiol.2014.270892. PMID: 24665101. PMCID: PMC4214653.

21. Camilleri M, Shin A, Busciglio I, et al. 2014; Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion. Am J Physiol Gastrointest Liver Physiol. 307:G508–G516. DOI: 10.1152/ajpgi.00178.2014. PMID: 25012842. PMCID: PMC4154122.

22. Camilleri M, Klee EW, Shin A, et al. 2014; Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit. Am J Physiol Gastrointest Liver Physiol. 306:G13–26. DOI: 10.1152/ajpgi.00294.2013. PMID: 24200957. PMCID: PMC3920085.

23. Keely SJ, Urso A, Ilyaskin AV, et al. 2022; Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels. Am J Physiol Gastrointest Liver Physiol. 322:G201–G222. DOI: 10.1152/ajpgi.00125.2021. PMID: 34755536. PMCID: PMC8782647.

24. Camilleri M, Vijayvargiya P. 2020; The role of bile acids in chronic diarrhea. Am J Gastroenterol. 115:1596–1603. DOI: 10.14309/ajg.0000000000000696. PMID: 32558690. PMCID: PMC7541465.

25. Magnus Y, BouSaba J, Sannaa W, McKinzie S, Busciglio I, Camilleri M. 2022; Bile acid diarrhea is associated with increased intestinal permeability compared with irritable bowel syndrome-diarrhea. Gastroenterology. 162:1343–1345.e1. DOI: 10.1053/j.gastro.2021.12.243. PMID: 34922946. PMCID: PMC8934275.

26. Farrugia A, Arasaradnam R. 2020; Bile acid diarrhoea: pathophysiology, diagnosis and management. Frontline Gastroenterol. 12:500–507. DOI: 10.1136/flgastro-2020-101436. PMID: 34712468. PMCID: PMC8515273.

27. Wells JE, Williams KB, Whitehead TR, Heuman DM, Hylemon PB. 2003; Development and application of a polymerase chain reaction assay for the detection and enumeration of bile acid 7alpha-dehydroxylating bacteria in human feces. Clin Chim Acta. 331:127–134. DOI: 10.1016/S0009-8981(03)00115-3. PMID: 12691873.

28. Kitahara M, Takamine F, Imamura T, Benno Y. 2000; Assignment of Eubacterium sp. VPI 12708 and related strains with high bile acid 7alpha-dehydroxylating activity to Clostridium scindens and proposal of Clostridium hylemonae sp. nov., isolated from human faeces. Int J Syst Evol Microbiol. 50:971–978. DOI: 10.1099/00207713-50-3-971. PMID: 10843034.

29. Min YW, Rezaie A, Pimentel M. 2022; Bile acid and gut microbiota in irritable bowel syndrome. J Neurogastroenterol Motil. 28:549–561. DOI: 10.5056/jnm22129. PMID: 36250362. PMCID: PMC9577585.

30. Camilleri M, Carlson P, BouSaba J, et al. 2023; Comparison of biochemical, microbial and mucosal mRNA expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea. Gut. 72:54–65. DOI: 10.1136/gutjnl-2022-327471. PMID: 35580964. PMCID: PMC9669287.

31. Dior M, Delagrèverie H, Duboc H, et al. 2016; Interplay between bile acid metabolism and microbiota in irritable bowel syndrome. Neurogastroenterol Motil. 28:1330–1340. DOI: 10.1111/nmo.12829. PMID: 27060367.

32. Zhao L, Yang W, Chen Y, et al. 2020; A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome. J Clin Invest. 130:438–450. DOI: 10.1172/JCI130976. PMID: 31815740. PMCID: PMC6934182.

33. Walters JR, Marchesi JR. 2020; Chronic diarrhea, bile acids, and Clostridia. J Clin Invest. 130:77–79. DOI: 10.1172/JCI133117. PMID: 31815741. PMCID: PMC6934195.

34. Sagar NM, Duboc H, Kay GL, et al. 2020; The pathophysiology of bile acid diarrhoea: differences in the colonic microbiome, metabolome and bile acids. Sci Rep. 10:20436. DOI: 10.1038/s41598-020-77374-7. PMID: 33235223. PMCID: PMC7686486.

35. Wedlake L, A'Hern R, Russell D, Thomas K, Walters JR, Andreyev HJ. 2009; Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 30:707–717. DOI: 10.1111/j.1365-2036.2009.04081.x. PMID: 19570102.

36. Valentin N, Camilleri M, Altayar O, et al. 2016; Biomarkers for bile acid diarrhoea in functional bowel disorder with diarrhoea: a systematic review and meta-analysis. Gut. 65:1951–1959. DOI: 10.1136/gutjnl-2015-309889. PMID: 26347530.

37. Fine KD, Schiller LR. 1999; AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology. 116:1464–1486. DOI: 10.1016/S0016-5085(99)70513-5. PMID: 10348832.

38. Walters JR, Pattni SS. 2010; Managing bile acid diarrhoea. Therap Adv Gastroenterol. 3:349–357. DOI: 10.1177/1756283X10377126. PMID: 21180614. PMCID: PMC3002596.

39. Slattery SA, Niaz O, Aziz Q, Ford AC, Farmer AD. 2015; Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther. 42:3–11. DOI: 10.1111/apt.13227. PMID: 25913530.

40. Costa S, Gattoni S, Nicolardi ML, et al. 2021; Prevalence and clinical features of bile acid diarrhea in patients with chronic diarrhea. J Dig Dis. 22:108–112. DOI: 10.1111/1751-2980.12969. PMID: 33438795.

41. Lenicek M, Duricova D, Komarek V, et al. 2011; Bile acid malabsorption in inflammatory bowel disease: assessment by serum markers. Inflamm Bowel Dis. 17:1322–1327. DOI: 10.1002/ibd.21502. PMID: 21058331.

42. Nyhlin H, Merrick MV, Eastwood MA. 1994; Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT. Gut. 35:90–93. DOI: 10.1136/gut.35.1.90. PMID: 8307458. PMCID: PMC1374639.

43. Farahmandfar MR, Chabok M, Alade M, Bouhelal A, Patel B. 2012; Post-cholecystectomy Diarrhoea: a systematic review. Surg Sci. 3:19988. DOI: 10.4236/ss.2012.36065.

44. Yueh TP, Chen FY, Lin TE, Chuang MT. 2014; Diarrhea after laparoscopic cholecystectomy: associated factors and predictors. Asian J Surg. 37:171–177. DOI: 10.1016/j.asjsur.2014.01.008. PMID: 24647139.

45. Fernandez-Bañares F, Esteve M, Salas A, et al. 2001; Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea. Dig Dis Sci. 46:2231–2238. DOI: 10.1023/A:1011927302076. PMID: 11680602.

46. Marteau P, Lavergne-Slove A, Lemann M, et al. 1997; Primary ileal villous atrophy is often associated with microscopic colitis. Gut. 41:561–564. DOI: 10.1136/gut.41.4.561. PMID: 9391260. PMCID: PMC1891516.

47. Einarsson K, Eusufzai S, Johansson U, Löfberg R, Theodorsson E, Veress B. 1992; Villous atrophy of distal ileum and lymphocytic colitis in a woman with bile acid malabsorption. Eur J Gastroenterol Hepatol. 4:585–590.

48. Phillips F, Muls AC, Lalji A, Andreyev HJ. 2015; Are bile acid malabsorption and bile acid diarrhoea important causes of loose stool complicating cancer therapy? Colorectal Dis. 17:730–734. DOI: 10.1111/codi.12932. PMID: 25728737.

49. Lyutakov I, Ursini F, Penchev P, et al. 2019; Methods for diagnosing bile acid malabsorption: a systematic review. BMC Gastroenterol. 19:185. DOI: 10.1186/s12876-019-1102-1. PMID: 31726982. PMCID: PMC6854889.

50. Shin A, Camilleri M, Vijayvargiya P, et al. 2013; Bowel functions, fecal unconjugated primary and secondary bile acids, and colonic transit in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 11:1270–1275.e1. DOI: 10.1016/j.cgh.2013.04.020. PMID: 23639599. PMCID: PMC3778140.

51. Wong BS, Camilleri M, Carlson P, et al. 2012; Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 10:1009–1015.e3. DOI: 10.1016/j.cgh.2012.05.006. PMID: 22610000. PMCID: PMC3565429.

52. Vijayvargiya P, Camilleri M, Chedid V, et al. 2019; Analysis of fecal primary bile acids detects increased stool weight and colonic transit in patients with chronic functional diarrhea. Clin Gastroenterol Hepatol. 17:922–929.e2. DOI: 10.1016/j.cgh.2018.05.050. PMID: 29902647. PMCID: PMC6291372.

53. Vijayvargiya P, Camilleri M, Burton D, Busciglio I, Lueke A, Donato LJ. 2019; Bile and fat excretion are biomarkers of clinically significant diarrhoea and constipation in irritable bowel syndrome. Aliment Pharmacol Ther. 49:744–758. DOI: 10.1111/apt.15106. PMID: 30740753.

54. Donato LJ, Lueke A, Kenyon SM, Meeusen JW, Camilleri M. 2018; Description of analytical method and clinical utility of measuring serum 7-alpha-hydroxy-4-cholesten-3-one (7aC4) by mass spectrometry. Clin Biochem. 52:106–111. DOI: 10.1016/j.clinbiochem.2017.10.008. PMID: 29051033.

55. Arasaradnam RP, Brown S, Forbes A, et al. 2018; Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut. 67:1380–1399. DOI: 10.1136/gutjnl-2017-315909. PMID: 29653941. PMCID: PMC6204957.

56. Camilleri M. 2014; Advances in understanding of bile acid diarrhea. Expert Rev Gastroenterol Hepatol. 8:49–61. DOI: 10.1586/17474124.2014.851599. PMID: 24410472. PMCID: PMC4211077.

57. Vijayvargiya P, Camilleri M, Carlson P, et al. 2017; Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea. Aliment Pharmacol Ther. 46:581–588. DOI: 10.1111/apt.14214. PMID: 28691284. PMCID: PMC5555810.

58. Pattni SS, Brydon WG, Dew T, et al. 2013; Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention. Aliment Pharmacol Ther. 38:967–976. DOI: 10.1111/apt.12466. PMID: 23981126.

59. Vítek L. 2015; Bile acid malabsorption in inflammatory bowel disease. Inflamm Bowel Dis. 21:476–483. DOI: 10.1097/MIB.0000000000000193. PMID: 25248001.

60. Sauter GH, Münzing W, von Ritter C, Paumgartner G. 1999; Bile acid malabsorption as a cause of chronic diarrhea: diagnostic value of 7alpha-hydroxy-4-cholesten-3-one in serum. Dig Dis Sci. 44:14–19. DOI: 10.1023/A:1026681512303. PMID: 9952217.

61. Vijayvargiya P, Camilleri M, Shin A, Saenger A. 2013; Methods for diagnosis of bile acid malabsorption in clinical practice. Clin Gastroenterol Hepatol. 11:1232–1239. DOI: 10.1016/j.cgh.2013.04.029. PMID: 23644387. PMCID: PMC3783593.

62. Wilcox C, Turner J, Green J. 2014; Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. Aliment Pharmacol Ther. 39:923–939. DOI: 10.1111/apt.12684. PMID: 24602022.

63. Orekoya O, McLaughlin J, Leitao E, Johns W, Lal S, Paine P. 2015; Quantifying bile acid malabsorption helps predict response and tailor sequestrant therapy. Clin Med (Lond). 15:252–257. DOI: 10.7861/clinmedicine.15-3-252. PMID: 26031975. PMCID: PMC4953109.

64. Savarino E, Zingone F, Barberio B, et al. 2022; Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J. 10:556–584. DOI: 10.1002/ueg2.12259. PMID: 35695704. PMCID: PMC9278595.

65. Sadowski DC, Camilleri M, Chey WD, et al. 2020; Canadian association of gastroenterology clinical practice guideline on the management of bile acid diarrhea. J Can Assoc Gastroenterol. 3:e10–e27. DOI: 10.1093/jcag/gwz038. PMID: 32010878. PMCID: PMC6985689.

66. Jackson A, Lalji A, Kabir M, et al. 2017; The efficacy of a low-fat diet to manage the symptoms of bile acid malabsorption - outcomes in patients previously treated for cancer. Clin Med (Lond). 17:412–418. DOI: 10.7861/clinmedicine.17-5-412. PMID: 28974589. PMCID: PMC6301937.

67. Watson L, Lalji A, Bodla S, Muls A, Andreyev HJ, Shaw C. 2015; Management of bile acid malabsorption using low-fat dietary interventions: a useful strategy applicable to some patients with diarrhoea-predominant irritable bowel syndrome? Clin Med (Lond). 15:536–540. DOI: 10.7861/clinmedicine.15-6-536. PMID: 26621941. PMCID: PMC4953254.

68. Staels B, Handelsman Y, Fonseca V. 2010; Bile acid sequestrants for lipid and glucose control. Curr Diab Rep. 10:70–77. DOI: 10.1007/s11892-009-0087-5. PMID: 20425070. PMCID: PMC2821506.

69. Barkun AN, Love J, Gould M, Pluta H, Steinhart H. 2013; Bile acid malabsorption in chronic diarrhea: pathophysiology and treatment. Can J Gastroenterol. 27:653–659. DOI: 10.1155/2013/485631. PMID: 24199211. PMCID: PMC3816948.

70. Ruiz-Campos L, Gisbert JP, Ysamat M, et al. 2019; Systematic review with meta-analysis: the prevalence of bile acid malabsorption and response to colestyramine in patients with chronic watery diarrhoea and previous cholecystectomy. Aliment Pharmacol Ther. 49:242–250. DOI: 10.1111/apt.15099. PMID: 30585336.

71. Beigel F, Teich N, Howaldt S, et al. 2014; Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn's disease: a randomized, double-blind, placebo-controlled study. J Crohns Colitis. 8:1471–1479. DOI: 10.1016/j.crohns.2014.05.009. PMID: 24953836.

72. Bajor A, Törnblom H, Rudling M, Ung KA, Simrén M. 2015; Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS. Gut. 64:84–92. DOI: 10.1136/gutjnl-2013-305965. PMID: 24727487.

73. Fernández-Bañares F, Rosinach M, Piqueras M, et al. 2015; Randomised clinical trial: colestyramine vs. hydroxypropyl cellulose in patients with functional chronic watery diarrhoea. Aliment Pharmacol Ther. 41:1132–1140. DOI: 10.1111/apt.13193. PMID: 25858478.

74. Camilleri M, Acosta A, Busciglio I, et al. 2015; Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 41:438–448. DOI: 10.1111/apt.13065. PMID: 25594801. PMCID: PMC4493894.

75. Vijayvargiya P, Camilleri M, Carlson P, et al. 2020; Effects of colesevelam on bowel symptoms, biomarkers, and colonic mucosal gene expression in patients with bile acid diarrhea in a randomized trial. Clin Gastroenterol Hepatol. 18:2962–2970.e6. DOI: 10.1016/j.cgh.2020.02.027. PMID: 32088296. PMCID: PMC7442687.

76. Wedlake L, Thomas K, Lalji A, Anagnostopoulos C, Andreyev HJ. 2009; Effectiveness and tolerability of colesevelam hydrochloride for bile-acid malabsorption in patients with cancer: a retrospective chart review and patient questionnaire. Clin Ther. 31:2549–2558. DOI: 10.1016/j.clinthera.2009.11.027. PMID: 20109999.

77. Camilleri M. 2016; Drug-resin drug interactions in patients with delayed gastric emptying: What is optimal time window for drug administration? Neurogastroenterol Motil. 28:1268–1271. DOI: 10.1111/nmo.12823. PMID: 26987693. PMCID: PMC4956542.

78. Knodel LC, Talbert RL. 1987; Adverse effects of hypolipidaemic drugs. Med Toxicol. 2:10–32. DOI: 10.1007/BF03259858. PMID: 3547004.

79. Kårhus ML, Brønden A, Forman JL, et al. 2022; Safety and efficacy of liraglutide versus colesevelam for the treatment of bile acid diarrhoea: a randomised, double-blind, active-comparator, non-inferiority clinical trial. Lancet Gastroenterol Hepatol. 7:922–931. DOI: 10.1016/S2468-1253(22)00198-4. PMID: 35868334.

80. Mroz MS, Keating N, Ward JB, et al. 2014; Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo. Gut. 63:808–817. DOI: 10.1136/gutjnl-2013-305088. PMID: 23916961.

81. Walters JR, Johnston IM, Nolan JD, Vassie C, Pruzanski ME, Shapiro DA. 2015; The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid. Aliment Pharmacol Ther. 41:54–64. DOI: 10.1111/apt.12999. PMID: 25329562.

82. Kulkarni AV, Tevethia HV, Arab JP, et al. 2021; Efficacy and safety of obeticholic acid in liver disease-A systematic review and metaanalysis. Clin Res Hepatol Gastroenterol. 45:101675. DOI: 10.1016/j.clinre.2021.101675. PMID: 33722778.

83. Camilleri M, Nord SL, Burton D, et al. 2020; Randomised clinical trial: significant biochemical and colonic transit effects of the farnesoid X receptor agonist tropifexor in patients with primary bile acid diarrhoea. Aliment Pharmacol Ther. 52:808–820. DOI: 10.1111/apt.15967. PMID: 32702169.