Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus
| Autor: | Sena Bluemel, Samuel B. Ho, Patrick M. Gillevet, Karen E. Nelson, Jun Xu, Masoumeh Sikaroodi, Derrick E. Fouts, Hendrik Vilstrup, Cristina Llorente, Jessica DePew, Xin Du, Peter Uhd Jepsen, Lirui Wang, Hui J. Wang, David A. Brenner, Mitchell L. Schubert, Tatiana Kisseleva, Bernd Schnabl, Tatsuo Inamine, Jasmohan S. Bajaj, Rohit Loomba, Henrik Toft Sørensen |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Alcoholic liver disease Cirrhosis General Physics and Astronomy Pharmacology Inbred C57BL Chronic liver disease Oral and gastrointestinal Hepatitis Alcohol Use and Health Substance Misuse Mice Liver disease 0302 clinical medicine Non-alcoholic Fatty Liver Disease 2.1 Biological and endogenous factors Aetiology lcsh:Science Multidisciplinary Liver Disease Incidence Liver Diseases Microbiota Fatty liver Alcoholic 3. Good health Intestines Alcoholism Liver Biochemistry Disease Progression Female 030211 gastroenterology & hepatology medicine.drug_class Science Chronic Liver Disease and Cirrhosis Proton-pump inhibitor Biology Article General Biochemistry Genetics and Molecular Biology Gastric Acid 03 medical and health sciences Genetics Journal Article medicine Animals Humans Liver Diseases Alcoholic Proton Pump Inhibitors General Chemistry medicine.disease Good Health and Well Being 030104 developmental biology Gastric acid lcsh:Q Steatohepatitis Digestive Diseases Enterococcus |
| Zdroj: | Nature Communications, vol 8, iss 1 Llorente, C, Jepsen, P, Inamine, T, Wang, L, Bluemel, S, Wang, H J, Loomba, R, Bajaj, J S, Schubert, M L, Sikaroodi, M, Gillevet, P M, Xu, J, Kisseleva, T, Ho, S B, DePew, J, Du, X, Sørensen, H T, Vilstrup, H, Nelson, K E, Brenner, D A, Fouts, D E & Schnabl, B 2017, ' Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus ', Nature Communications, vol. 8, no. 1, 837 . https://doi.org/10.1038/s41467-017-00796-x Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017) Nature Communications |
| Popis: | Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease. Proton pump inhibitors (PPIs) reduce gastric acid secretion and modulate gut microbiota composition. Here Llorente et al. show that PPIs induce bacterial overgrowth of enterococci, which, in turn, exacerbate ethanol-induced liver disease both in mice and humans. |
| Databáze: | OpenAIRE |
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