Absence of the intestinal microbiota exacerbates hepatobiliary disease in a murine model of primary sclerosing cholangitis

Hepatology

Volumn 63, Issue 1, 2016, Pages 185-196

  Tabibian, James H ^a   O'Hara, Steven P ^a   Trussoni, Christy E ^a   Tietz, Pamela S ^a   Splinter, Patrick L ^a   Mounajjed, Taofic ^a   Hagey, Lee R ^b   Larusso, Nicholas F ^a  

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; BILE ACID; BILIRUBIN; CYCLIN DEPENDENT KINASE INHIBITOR 2A; HYDROXYPROLINE; INTERLEUKIN 10; URSODEOXYCHOLIC ACID;

ALKALINE PHOSPHATASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; BLOOD BIOCHEMISTRY; CONTROLLED STUDY; DISEASE EXACERBATION; DISEASE SEVERITY; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; HEPATOBILIARY DISEASE; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE MICROSCOPY; IN VITRO STUDY; INFLAMMATION; INTESTINE FLORA; KNOCKOUT MOUSE; LIVER FIBROSIS; LIVER HISTOLOGY; MALE; MORPHOMETRICS; MOUSE; NONHUMAN; PATHOGENESIS; PRIMARY SCLEROSING CHOLANGITIS; PRIORITY JOURNAL; SENESCENCE; ANIMAL; CHOLANGITIS, SCLEROSING; DISEASE COURSE; DISEASE MODEL; PHYSIOLOGY;

ANIMALS; CHOLANGITIS, SCLEROSING; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; FEMALE; GASTROINTESTINAL MICROBIOME; MALE; MICE; MICE, KNOCKOUT;

EID: 84952637577     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.27927     Document Type: Article

References (50)

1. Tabibian JH, Lindor KD. Primary sclerosing cholangitis: a review and update on therapeutic developments. Expert Rev Gastroenterol Hepatol 2013;7:103-114.
2. Weismuller TJ, Wedemeyer J, Kubicka S, Strassburg CP, Manns MP. The challenges in primary sclerosing cholangitis-aetiopathogenesis, autoimmunity, management and malignancy. J Hepatol 2008;48(Suppl 1):S38-S57.
3. Farrant JM, Hayllar KM, Wilkinson ML, Karani J, Portmann BC, Westaby D, et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991;100:1710-1717.
4. Tabibian JH, Lindor KD. Challenges of cholangiocarcinoma detection in patients with primary sclerosing cholangitis. J Anal Oncol 2012;1:50-55.
5. Bangarulingam SY, Bjornsson E, Enders F, Barr Fritcher EG, Gores G, Halling KC, et al. Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis. Hepatology 2010;51:174-180.
6. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010;51:660-678.
7. Beuers U, Boberg KM, Chapman RW, Chazouillères O, Invernizzi P, Jones DE, et al. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009;51:237-267.
8. Brandsaeter B, Friman S, Broome U, Isoniemi H, Olausson M, Backman L, et al. Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries. Scand J Gastroenterol 2003;38:1176-1183.
9. Ali JM, Bonomo L, Brais R, Griffiths WJ, Lomas DJ, Huguet EL, et al. Outcomes and diagnostic challenges posed by incidental cholangiocarcinoma after liver transplantation. Transplantation 2011;91:1392-1397.
10. Levy C, Lindor KD. Primary sclerosing cholangitis: epidemiology, natural history, and prognosis. Semin Liver Dis 2006;26:22-30.
11. DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol 2011;8:523-531.
12. Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013;62:531-539.
13. Ngu JH, Gearry RB, Wright AJ, Stedman CA. Inflammatory bowel disease is associated with poor outcomes of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2011;9:1092-1097; quiz, e1135.
14. Wiesner RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology 1980;79:200-206.
15. Fickert P, Fuchsbichler A, Wagner M, Zollner G, Kaser A, Tilg H, et al. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 2004;127:261-274.
16. Tabibian JH, Macura SI, O'Hara SP, Fidler JL, Glockner JF, Takahashi N, et al. Micro-computed tomography and nuclear magnetic resonance imaging for noninvasive, live-mouse cholangiography. Lab Invest 2013;93:733-743.
17. Smit JJ, Schinkel AH, Oude Elferink RP, Groen AK, Wagenaar E, van Deemter L, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 1993;75:451-462.
18. Tabibian JH, O'Hara SP, Splinter PL, Trussoni CE, Larusso NF. Cholangiocyte senescence via N-Ras activation is a characteristic of primary sclerosing cholangitis. Hepatology 2014;59:2263-2275.
19. Taconic Animal Health Standards [Internet]. Germ-free mice; 2013 [cited 2014 Jan 7]. Available at: http://info.taconic.com/hubfs/Collateral/Brochures_And_Sell_Sheets/Taconic-Biosciences-health-standards.pdf.
20. Heuman DM, Hylemon PB, Vlahcevic ZR. Regulation of bile acid synthesis. III. Correlation between biliary bile salt hydrophobicity index and the activities of enzymes regulating cholesterol and bile acid synthesis in the rat. J Lipid Res 1989;30:1161-1171.
21. Yamaguchi K, Yang L, McCall S, Huang J, Yu XX, Pandey SK, et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 2007;45:1366-1374.
22. Bona S, Filippin LI, Di Naso FC, de David C, Valiatti B, Isoppo Schaun M, et al. Effect of antioxidant treatment on fibrogenesis in rats with carbon tetrachloride-induced cirrhosis. ISRN Gastroenterol 2012;2012:762920.
23. de Planell-Saguer M, Rodicio MC, Mourelatos Z. Rapid in situ codetection of noncoding RNAs and proteins in cells and formalin-fixed paraffin-embedded tissue sections without protease treatment. Nat Protoc 2010;5:1061-1073.
24. Banales JM, Saez E, Uriz M, Sarvide S, Urribarri AD, Splinter P, et al. Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology 2012;56:687-697.
25. Abrams GD, Bauer H, Sprinz H. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest 1963;12:355-364.
26. Ukena SN, Singh A, Dringenberg U, Engelhardt R, Seidler U, Hansen W, et al. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity. PLoS One 2007;2:e1308.
27. Louis H, Van Laethem JL, Wu W, Quertinmont E, Degraef C, Van den Berg K, et al. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Hepatology 1998;28:1607-1615.
28. Pohl J, Ring A, Stremmel W, Stiehl A. The role of dominant stenoses in bacterial infections of bile ducts in primary sclerosing cholangitis. Eur J Gastroenterol Hepatol 2006;18:69-74.
29. Olsson R, Bjornsson E, Backman L, Friman S, Hockerstedt K, Kaijser B, et al. Bile duct bacterial isolates in primary sclerosing cholangitis: a study of explanted livers. J Hepatol 1998;28:426-432.
30. Hiramatsu K, Harada K, Tsuneyama K, Sasaki M, Fujita S, Hashimoto T, et al. Amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene in gallbladder bile from patients with primary biliary cirrhosis. J Hepatol 2000;33:9-18.
31. Chen XM, O'Hara SP, Nelson JB, Splinter PL, Small AJ, Tietz PS, et al. Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-kappaB. J Immunol 2005;175:7447-7456.
32. Sasatomi K, Noguchi K, Sakisaka S, Sata M, Tanikawa K. Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis. J Hepatol 1998;29:409-416.
33. Mueller T, Beutler C, Pico AH, Shibolet O, Pratt DS, Pascher A, et al. Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis. Liver Int 2011;31:1574-1588.
34. Lichtman SN, Keku J, Clark RL, Schwab JH, Sartor RB. Biliary tract disease in rats with experimental small bowel bacterial overgrowth. Hepatology 1991;13:766-772.
35. Yamada S, Ishii M, Liang LS, Yamamoto T, Toyota T. Small duct cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine in rats. J Gastroenterol 1994;29:631-636.
36. Tabibian JH, Talwalkar JA, Lindor KD. Role of the microbiota and antibiotics in primary sclerosing cholangitis. Biomed Res Int 2013;2013:389537.
37. Tabibian JH, Weeding E, Jorgensen RA, Petz JL, Keach JC, Talwalkar JA, et al. Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis-a pilot study. Aliment Pharmacol Ther 2013;37:604-612.
38. Cesaro C, Tiso A, Del Prete A, Cariello R, Tuccillo C, Cotticelli G, et al. Gut microbiota and probiotics in chronic liver diseases. Dig Liver Dis 2011;43:431-438.
39. Mazagova M, Wang L, Anfora AT, Wissmueller M, Lesley SA, Miyamoto Y, et al. Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice. FASEB J 2015;29:1043-1055.
40. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004;118:229-241.
41. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 2012;336:489-493.
42. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science 2012;336:1268-1273.
43. Burton DG. Cellular senescence, ageing and disease. Age (Dordr) 2009;31:1-9.
44. Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 2013;123:966-972.
45. Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008;6:2853-2868.
46. Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 2008;133:1006-1018.
47. Van Nieuwkerk CM, Elferink RP, Groen AK, Ottenhoff R, Tytgat GN, Dingemans KP, et al. Effects of Ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology 1996;111:165-171.
48. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Weiglein AH, Lammert F, et al. Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles. Gastroenterology 2002;123:1238-1251.
49. Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007;445:656-660.
50. Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011;479:547-551.