Mikrobiom & NASH – enge Komplizen in der Progression von Fettlebererkrankungen

Zusammenfassung

Einhergehend mit der steigenden Prävalenz von Übergewicht, metabolischem Syndrom und Typ-2-Diabetes nehmen nicht-alkoholische Fettlebererkrankungen (NAFLD) stark zu und stellen eine große Herausforderung in der Gastroenterologie dar. Viele Studien konnten nachweisen, dass das Mikrobiom in einem engen Zusammenhang mit der Progression von ernährungsbedingten Krankheitsbildern, insbesondere auch von Fettlebererkrankungen, steht. Veränderungen in der Quantität und Qualität der Darmflora, allgemein als Dysbiose bezeichnet, bedingen veränderte Metabolisierung von Nahrungsmitteln, erhöhte Permeabilität der Darmbarriere („leaky gut“) und konsekutiv Entzündungsprozesse in der Leber. Dies begünstigt sowohl das Fortschreiten von Adipositas und metabolischen Störungen als auch von NAFLD zur nicht-alkoholischen Steatohepatitis (NASH), hepatischen Fibrose, Leberzirrhose und hepatozellulärem Karzinom (HCC). Wichtige molekulare Mechanismen beinhalten mikrobielle Stoffwechselprodukte, mikrobielle und endogene Signalstoffe (sogenannte PAMPs/DAMPs) sowie Gallensäuren. Essenzielle zelluläre Mechanismen umfassen immunologische Zellen in Darm und Leber, insbesondere Makrophagen und Kupffer-Zellen, sowie Darmepithelzellen und Hepatozyten als zentrale Regulatoren des Stoffwechsels. In dieser Übersicht wollen wir anhand aktueller wissenschaftlicher Arbeiten und klinischer Studien kurz auf die relevanten Spezies des humanen Mikrobioms eingehen, die mikrobielle Analytik erläutern, die wichtigsten molekularen Zusammenhänge zwischen Mikrobiom und NAFLD/NASH erklären und schlussendlich Möglichkeiten der Mikrobiom-modulierenden Therapie zur Behandlung von Fettlebererkrankungen darlegen.

Abstract

Along with the increasing prevalence of obesity, metabolic syndrome and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and poses a major challenge for gastroenterologists. Many studies have demonstrated that the microbiome is closely associated with the progression of nutrition-related diseases, especially of fatty liver disease. Changes in the quantity and quality of the intestinal flora, commonly referred to as dysbiosis, result in altered food metabolism, increased permeability of the intestinal barrier (“leaky gut”) and consecutive inflammatory processes in the liver. This favors both the progression of obesity and metabolic disorders as well as NAFLD towards non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Important molecular mechanisms include microbial metabolites, microbial and endogenous signaling substances (so-called PAMPs/DAMPs) as well as bile acids. Essential cellular mechanisms include immune cells in the gut and liver, especially macrophages and Kupffer cells, as well as intestinal epithelial cells and hepatocytes as central regulators of metabolism. In this review article, we briefly summarize the relevant species of the human microbiome, describe the microbial analytics, explain the most important molecular relationships between microbiome and NAFLD/NASH, and finally the opportunities and challenges of microbiome-modulating therapy for the treatment of fatty liver disease.

Schlüsselwörter

Darm - Leber - Mikrobiom - Fettleber - NASH

Key words

microbiome - dysbiosis - gut-liver axis - steatosis - liver fibrosis

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