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Int. J. Mol. Sci. 2019, 20(2), 308; https://doi.org/10.3390/ijms20020308

Intestinal Microbiota Protects against MCD Diet-Induced Steatohepatitis

1
Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany
2
Department of Pathology, Klinikum Braunschweig, 38118 Braunschweig, Germany
3
Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands
*
Author to whom correspondence should be addressed.
Received: 14 November 2018 / Revised: 14 December 2018 / Accepted: 8 January 2019 / Published: 14 January 2019
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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. View Full-Text
Keywords: NASH; Gut-liver-Axis; microbiota; MCD NASH; Gut-liver-Axis; microbiota; MCD
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Schneider, K.M.; Mohs, A.; Kilic, K.; Candels, L.S.; Elfers, C.; Bennek, E.; Schneider, L.B.; Heymann, F.; Gassler, N.; Penders, J.; Trautwein, C. Intestinal Microbiota Protects against MCD Diet-Induced Steatohepatitis. Int. J. Mol. Sci. 2019, 20, 308.

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