Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg

被引:236
作者
Arab, Juan P. [1 ,2 ]
Martin-Mateos, Rosa M. [1 ]
Shah, Vijay H. [1 ]
机构
[1] Mayo Clin, Div Gastroenterol & Hepatol, 200 First St SW, Rochester, MN 55905 USA
[2] Pontificia Univ Catolica Chile, Dept Gastroenterol, Escuela Med, Santiago, Chile
关键词
Gut-liver axis; Cirrhosis; Portal hypertension; Microbiota; Translocation; LPS; Endotoxemia; Bile acids; NONALCOHOLIC FATTY LIVER; PRIMARY SCLEROSING CHOLANGITIS; PROTON PUMP INHIBITORS; SPONTANEOUS BACTERIAL PERITONITIS; PATTERN-RECOGNITION RECEPTORS; SYSTEMS BIOLOGY ANALYSIS; BILE-ACID RECEPTOR; HEPATIC-ENCEPHALOPATHY; INTESTINAL MICROBIOTA; PROBIOTIC VSLNUMBER-3;
D O I
10.1007/s12072-017-9798-x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
The term gut-liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a "chicken and egg" situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.
引用
收藏
页码:S24 / S33
页数:10
相关论文
共 114 条
[1]
INACTIVATION OF KUPFFER CELLS PREVENTS EARLY ALCOHOL-INDUCED LIVER-INJURY [J].
ADACHI, Y ;
BRADFORD, BU ;
GAO, WS ;
BOJES, HK ;
THURMAN, RG .
HEPATOLOGY, 1994, 20 (02) :453-460
[2]
ANTIBIOTICS PREVENT LIVER-INJURY IN RATS FOLLOWING LONG-TERM EXPOSURE TO ETHANOL [J].
ADACHI, Y ;
MOORE, LE ;
BRADFORD, BU ;
GAO, WS ;
THURMAN, RG .
GASTROENTEROLOGY, 1995, 108 (01) :218-224
[3]
NALP3 forms an IL-lβ-Processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J].
Agostini, L ;
Martinon, F ;
Burns, K ;
McDermott, MF ;
Hawkins, PN ;
Tschopp, J .
IMMUNITY, 2004, 20 (03) :319-325
[4]
Pathogen recognition and innate immunity [J].
Akira, S ;
Uematsu, S ;
Takeuchi, O .
CELL, 2006, 124 (04) :783-801
[5]
Interleukin-6 Modulation of Intestinal Epithelial Tight Junction Permeability Is Mediated by JNK Pathway Activation of Claudin-2 Gene [J].
Al-Sadi, Rana ;
Ye, Dongmei ;
Boivin, Michel ;
Guo, Shuhong ;
Hashimi, Mariam ;
Ereifej, Lisa ;
Ma, Thomas Y. .
PLOS ONE, 2014, 9 (03)
[6]
Bile Acids and Nonalcoholic Fatty Liver Disease: Molecular Insights and Therapeutic Perspectives [J].
Arab, Juan P. ;
Karpen, Saul J. ;
Dawson, Paul A. ;
Arrese, Marco ;
Trauner, Michael .
HEPATOLOGY, 2017, 65 (01) :350-362
[7]
Innate Immunity and Inflammation in NAFLD/NASH [J].
Arrese, Marco ;
Cabrera, Daniel ;
Kalergis, Alexis M. ;
Feldstein, Ariel E. .
DIGESTIVE DISEASES AND SCIENCES, 2016, 61 (05) :1294-1303
[8]
Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis [J].
Bajaj, J. S. ;
Heuman, D. M. ;
Hylemon, P. B. ;
Sanyal, A. J. ;
Puri, P. ;
Sterling, R. K. ;
Luketic, V. ;
Stravitz, R. T. ;
Siddiqui, M. S. ;
Fuchs, M. ;
Thacker, L. R. ;
Wade, J. B. ;
Daita, K. ;
Sistrun, S. ;
White, M. B. ;
Noble, N. A. ;
Thorpe, C. ;
Kakiyama, G. ;
Pandak, W. M. ;
Sikaroodi, M. ;
Gillevet, P. M. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2014, 39 (10) :1113-1125
[9]
Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function [J].
Bajaj, Jasmohan S. ;
Cox, I. Jane ;
Betrapally, Naga S. ;
Heuman, Douglas M. ;
Schubert, Mitchell L. ;
Ratneswaran, Maiyuran ;
Hylemon, Phillip B. ;
White, Melanie B. ;
Daita, Kalyani ;
Noble, Nicole A. ;
Sikaroodi, Masoumeh ;
Williams, Roger ;
Crossey, Mary M. E. ;
Taylor-Robinson, Simon D. ;
Gillevet, Patrick M. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2014, 307 (10) :G951-G957
[10]
Altered profile of human gut microbiome is associated with cirrhosis and its complications [J].
Bajaj, Jasmohan S. ;
Heuman, Douglas M. ;
Hylemon, Phillip B. ;
Sanyal, Arun J. ;
White, Melanie B. ;
Monteith, Pamela ;
Noble, Nicole A. ;
Unser, Ariel B. ;
Daita, Kalyani ;
Fisher, Andmorgan R. ;
Sikaroodi, Masoumeh ;
Gillevet, Patrick M. .
JOURNAL OF HEPATOLOGY, 2014, 60 (05) :940-947