Advertisement

Mikrobiota und nichtalkoholische Fettlebererkrankung

  • A. Link
  • C. Thon
  • S. Sydor
  • A. CanbayEmail author
Schwerpunkt
  • 14 Downloads

Zusammenfassung

Die nichtalkoholische Fettlebererkrankung („non-alcoholic fatty liver disease“, NAFLD) ist in den letzten 10 Jahren verstärkt in den Fokus der Aufmerksamkeit gerückt. Durch die massive Zunahme von Adipositas, metabolischem Syndrom und deren negative Auswirkungen auf die Leber nimmt die Zahl der Patienten mit Lebererkrankungen wie der NAFLD oder dem hepatozellulären Karzinom („hepatocellular carcinoma“, HCC) stetig zu. Mittlerweile leiden etwa 25 % der Bevölkerung unter einer Leberverfettung. Für die Zukunft ist es wichtig, Mittel und Wege zu finden, diesen Trend aufzuhalten bzw. umzukehren. In diesem Zusammenhang kommt neben gesunder Ernährung, Gewichtsreduktion und sportlicher Aktivität insbesondere der Darmmikrobiota, vermutlich über die Darm-Leber-Achse, eine Schlüsselrolle bei der Entstehung und Progression von Lebererkrankungen zu. In diesem Review wird auf die aktuelle Evidenz mit Relevanz für die praktizierenden Ärzte eingegangen. Hier stellen die Autoren die wichtigsten Entwicklungen aus In-vivo- und translationaler Forschung vor und gehen auf die mögliche Bedeutung für die Therapie der NAFLD ein.

Schlüsselwörter

Lebererkrankungen Erkrankungen des Verdauungstrakts Hepatozelluläres Karzinom Tiermodelle Fäkale Mikrobiotatransplantation 

Microbiota and non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) has received increased attention during the last 10 years. Due to epidemic increases of obesity, metabolic syndrome and their negative effects on the liver, the number of patients with liver diseases including NAFLD or hepatocellular carcinoma (HCC) is steadily growing. Meanwhile, about 25% of the population suffer from fatty liver. In the future, it is crucial to identify the ways to stop and reverse this trend. In this context, in addition to the healthy diet, weight loss and physical activity especially the gut microbiota and the gut–liver axis play a key role in the development and progression of liver diseases. In this review, we provide the current scientific evidence to microbiota and NAFLD with a main focus on the relevance for practicing physicians. Here we present the most important developments from in vivo and translational research and address the potential relevance for the treatment of NAFLD.

Keywords

Liver diseases Digestive system diseases Hepatocellular carcinoma Animal models Fecal microbiota transplantion 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

A. Link und A. Canbay werden von der Wilhelm-Laupitz-Stiftung gefördert. C. Thon und S. Sydor geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Literatur

  1. 1.
    Chalasani N, Younossi Z, Lavine JE (2012) Erratum: The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 143(2):503CrossRefGoogle Scholar
  2. 2.
    NCD Risk Factor Collaboration (NCD-RisC) (2016) Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387(10026):1377–1396CrossRefGoogle Scholar
  3. 3.
    Garapati K, Vizuete J, Malakouti M, Gutierrez J, Camero A (2017) Perspectives on nonalcoholic fatty liver disease: An overview of present and future therapies. J Clin Transl Hepatol 5(1):67–75CrossRefGoogle Scholar
  4. 4.
    Buzzetti E, Pinzani M, Tsochatzis EA (2016) The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 65(8):1038–1048CrossRefGoogle Scholar
  5. 5.
    Takaki A, Kawai D, Yamamoto K (2013) Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int J Mol Sci 14(10):20704–20728CrossRefGoogle Scholar
  6. 6.
    Masarone M, Federico A, Abenavoli L, Loguercio C, Persico M (2014) Non alcoholic fatty liver: Epidemiology and natural history. Rev Recent Clin Trials 9(3):126–133CrossRefGoogle Scholar
  7. 7.
    Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P (2005) The natural history of nonalcoholic fatty liver disease: A population-based cohort study. Gastroenterology 129(1):113–121CrossRefGoogle Scholar
  8. 8.
    El-Kader SMA, Ashmawy EMSE-D (2015) Non-alcoholic fatty liver disease: The diagnosis and management. World J Hepatol 7(6):846CrossRefGoogle Scholar
  9. 9.
    Cheng DD, He C, Ai HH, Huang Y, Lu NH (2017) The possible role of Helicobacter pylori infection in non-alcoholic fatty liver disease. Front Microbiol.  https://doi.org/10.3389/fmicb.2017.00743 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wong RJ, Cheung R, Ahmed A (2014) Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology 59(6):2188–2195CrossRefGoogle Scholar
  11. 11.
    Hooper LV, Midtvedt T, Gordon JI (2002) How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 22(1):283–307CrossRefGoogle Scholar
  12. 12.
    Qin J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59–65CrossRefGoogle Scholar
  13. 13.
    Adams DH, Eksteen B, Curbishley SM (2008) Immunology of the gut and liver: A love/hate relationship. Gut 57(6):838–848CrossRefGoogle Scholar
  14. 14.
    Ivanov II, Honda K (2012) Intestinal commensal microbes as immune modulators. Cell Host Microbe 12(4):496–508CrossRefGoogle Scholar
  15. 15.
    Jiang W et al (2015) Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci Rep 5Google Scholar
  16. 16.
    Leung C, Rivera L, Furness JB, Angus PW (2016) The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 13(7):412–425CrossRefGoogle Scholar
  17. 17.
    Mouzaki M et al (2013) Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58(1):120–127CrossRefGoogle Scholar
  18. 18.
    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1031CrossRefGoogle Scholar
  19. 19.
    Le Roy T et al (2013) Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut 62(12):1787–1794CrossRefGoogle Scholar
  20. 20.
    Canbay A, Bechmann LP, Best J, Jochum C, Treichel U, Gerken G (2006) Crohn’s disease-induced non-alcoholic fatty liver disease (NAFLD) sensitizes for severe acute hepatitis B infection and liver failure. Z Gastroenterol 44(3):245–248CrossRefGoogle Scholar
  21. 21.
    Kälsch J et al (2013) Non-alcoholic steatohepatitis occurs in celiac disease and is associated with cellular stress. Z Gastroenterol 51(01):26–31CrossRefGoogle Scholar
  22. 22.
    Bashiardes S, Shapiro H, Rozin S, Shibolet O, Elinav E (2016) Non-alcoholic fatty liver and the gut microbiota. Mol Metab 5(9):782CrossRefGoogle Scholar
  23. 23.
    Jiang C et al (2015) Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest 125(1):386–402CrossRefGoogle Scholar
  24. 24.
    Dapito DH et al (2012) Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21(4):504–516CrossRefGoogle Scholar
  25. 25.
    Yoshimoto S et al (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499(7456):97–101CrossRefGoogle Scholar
  26. 26.
    Xie G et al (2017) Sex-dependent effects on gut microbiota regulate hepatic carcinogenic outcomes. Sci Rep 7:45232CrossRefGoogle Scholar
  27. 27.
    Zhou D et al (2017) Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci Rep 7(1):1529CrossRefGoogle Scholar
  28. 28.
    Liang Y et al (2018) Oral administration of compound probiotics ameliorates HFD-induced gut microbe dysbiosis and chronic metabolic inflammation via the G protein-coupled receptor 43 in non-alcoholic fatty liver disease rats. Probiotics Antimicrob Proteins.  https://doi.org/10.1007/s12602-017-9378-3 CrossRefPubMedGoogle Scholar
  29. 29.
    Ridaura VK et al (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341(6150):1241214CrossRefGoogle Scholar
  30. 30.
    van Best N, Jansen PL, Rensen SS (2015) The gut microbiota of nonalcoholic fatty liver disease: Current methods and their interpretation. Hepatol Int 9(3):406–415CrossRefGoogle Scholar
  31. 31.
    Bajaj JS et al (2014) Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol 60(5):940–947CrossRefGoogle Scholar
  32. 32.
    Pedersen HK et al (2016) Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535(7612):376–381CrossRefGoogle Scholar
  33. 33.
    Vrieze A et al (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143(4):913–916.e7CrossRefGoogle Scholar
  34. 34.
    Kootte RS et al (2017) Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab 26(4):611–619.e6CrossRefGoogle Scholar
  35. 35.
    Smillie CS et al (2018) Strain tracking reveals the determinants of bacterial engraftment in the human gut following fecal microbiota transplantation. Cell Host Microbe 23(2):229–240.e5CrossRefGoogle Scholar
  36. 36.
    Bajaj JS, Fagan A, Gavis EA, Kassam Z, Sikaroodi M, Gillevet PM (2019) Long-term outcomes after fecal microbiota transplant in cirrhosis. Gastroenterology.  https://doi.org/10.1053/j.gastro.2019.01.033 CrossRefPubMedGoogle Scholar
  37. 37.
    Wan Y et al (2019) Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: A 6-month randomised controlled-feeding trial. Gut.  https://doi.org/10.1136/gutjnl-2018-317609 CrossRefPubMedGoogle Scholar
  38. 38.
    Forslund K et al (2015) Disentangling the effects of type 2 diabetes and metformin on the human gut microbiota. Nature 528(7581):262–266CrossRefGoogle Scholar
  39. 39.
    Wu H et al (2017) Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med 23(7):850–858CrossRefGoogle Scholar
  40. 40.
    Brochado AR et al (2018) Species-specific activity of antibacterial drug combinations. Nature 559(7713):259–263CrossRefGoogle Scholar
  41. 41.
    Maier L et al (2018) Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555(7698):623–628CrossRefGoogle Scholar
  42. 42.
    Almeida A et al (2019) A new genomic blueprint of the human gut microbiota. Nature.  https://doi.org/10.1038/s41586-019-0965-1 CrossRefPubMedGoogle Scholar
  43. 43.
    Ott SJ et al (2016) Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology 152(4):799–811.e7CrossRefGoogle Scholar
  44. 44.
    Singh V et al (2018) Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell 175(3):679–694.e22CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Klinik für Gastroenterologie, Hepatologie und InfektiologieOtto-von-Guericke-Universität MagdeburgMagdeburgDeutschland

Personalised recommendations