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Liver tissue microbiome in NAFLD: next step in understanding the gut–liver axis?
  1. Herbert Tilg1,
  2. Remy Burcelin2,3,
  3. Valentina Tremaroli4
  1. 1Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
  2. 2Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1048, Toulouse, France
  3. 3Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: 'Intestinal Risk Factors, Diabetes, Dyslipidemia' F-31432, Toulouse Cedex 4, France
  4. 4Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
  1. Correspondence to Professor Herbert Tilg, Christian Doppler Research Laboratory and Dep, Innsbruck Medical University, Innsbruck 6020, Austria; herbert.tilg{at}i-med.ac.at

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The pathogenesis of non-alcoholic fatty liver disease (NAFLD), the most common global liver disease, is complex as multiple parallel hits drive this disorder. Whereas lipotoxicity, insulin resistance, inflammatory processes, oxidative stress and others reflect key components, studies from the past years have clearly shown that the gut microbiome might also substantially contribute to the evolution of NAFLD including its inflammatory component, that is, non-alcoholic steatohepatitis (NASH). Several studies from the last years have revealed alterations in the gut microbiome in people with NAFLD compared with healthy controls. NAFLD subjects accompanied by advanced fibrosis exhibit a gut microbiome signature with increased concentrations of Proteobacteria and Escherichia coli.1 Gut bacteria-derived metabolites such as phenylacetic acid and endotoxin are associated with degree of steatosis in female NAFLD patients and this metabolite, and the microbiota from NAFLD patients, induced hepatic lipid accumulation when given to mice.2 Therefore, evidence is increasing that the intestinal microbiota and its metabolites might play a crucial role in the pathogenesis of liver diseases including NAFLD.3

The liver is the key gatekeeper of blood flow from the portal vein draining the intestine and is constantly challenged by intestine-derived bacteria and bacterial components, such as endotoxin and other soluble molecules. Importantly, an intact intestinal epithelial barrier might protect the liver from bacterial …

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Footnotes

  • Contributors HT, RB and VT wrote the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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