Intestinal Microbiota Protects against MCD Diet-Induced Steatohepatitis

Kai Markus Schneider, Antje Mohs, Konrad Kilic, Lena Susanna Candels, Carsten Elfers, Eveline Bennek, Lukas Ben Schneider, Felix Heymann, Nikolaus Gassler, John Penders, Christian Trautwein*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Web of Science)

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in western countries, with a continuously rising incidence. Gut-liver communication and microbiota composition have been identified as critical drivers of the NAFLD progression. Hence, it has been shown that microbiota depletion can ameliorate high-fat diet or western-diet induced experimental Non-alcoholic steatohepatitis (NASH). However, its functional implications in the methionine-choline dietary model, remain incompletely understood. Here, we investigated the physiological relevance of gut microbiota in methionine-choline deficient (MCD) diet induced NASH. Experimental liver disease was induced by 8 weeks of MCD feeding in wild-type (WT) mice, either with or without commensal microbiota depletion, by continuous broad-spectrum antibiotic (AB) treatment. MCD diet induced steatohepatitis was accompanied by a reduced gut microbiota diversity, indicating intestinal dysbiosis. MCD treatment prompted macroscopic shortening of the intestine, as well as intestinal villi in histology. However, gut microbiota composition of MCD-treated mice, neither resembled human NASH, nor did it augment the intestinal barrier integrity or intestinal inflammation. In the MCD model, AB treatment resulted in increased steatohepatitis activity, compared to microbiota proficient control mice. This phenotype was driven by pronounced neutrophil infiltration, while AB treatment only slightly increased monocyte-derived macrophages (MoMF) abundance. Our data demonstrated the differential role of gut microbiota, during steatohepatitis development. In the context of MCD induced steatohepatitis, commensal microbiota was found to be hepatoprotective.

Original languageEnglish
Article number308
Pages (from-to)1-14
Number of pages14
JournalInternational journal of molecular sciences
Volume20
Issue number2
DOIs
Publication statusPublished - 2 Jan 2019

Keywords

  • NASH
  • Gut-liver-Axis
  • microbiota
  • MCD
  • FATTY LIVER-DISEASE
  • NONALCOHOLIC STEATOHEPATITIS
  • INSULIN-RESISTANCE
  • MICE
  • FIBROSIS
  • METHIONINE
  • DYSBIOSIS
  • CHOLINE
  • NAFLD

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