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The role of the gut microbiota in nonalcoholic fatty liver disease

Abstract

Important metabolic functions have been identified for the gut microbiota in health and disease. Several lines of evidence suggest a role for the gut microbiota in both the etiology of nonalcoholic fatty liver disease (NAFLD) and progression to its more advanced state, nonalcoholic steatohepatitis (NASH). Both NAFLD and NASH are strongly linked to obesity, type 2 diabetes mellitus and the metabolic syndrome and, accordingly, have become common worldwide problems. Small intestinal bacterial overgrowth of Gram-negative organisms could promote insulin resistance, increase endogenous ethanol production and induce choline deficiency, all factors implicated in NAFLD. Among the potential mediators of this association, lipopolysaccharide (a component of Gram-negative bacterial cell walls) exerts relevant metabolic and proinflammatory effects. Although the best evidence to support a role for the gut microbiota in NAFLD and NASH comes largely from animal models, data from studies in humans (albeit at times contradictory) is accumulating and could lead to new therapeutic avenues for these highly prevalent conditions.

Key Points

  • The gut microbiota can exert important metabolic effects relevant to obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD)

  • Several lines of evidence suggest a role for the gut microbiota, or its products, in the etiology and progression of NAFLD to nonalcoholic steatohepatitis (NASH)

  • Prominent among the potential mediators of these effects of the gut microbiota is lipopolysaccharide derived from Gram-negative bacteria

  • Lipopolysaccharide and other bacterial products have a number of metabolic and proinflammatory effects

  • Bacterial overgrowth in the small intestine is linked to NAFLD and NASH in animal models; its role in human NAFLD continues to be investigated

  • Modification of the gut microbiota may represent a new (though as yet unproven) strategy in the management of patients with NAFLD or NASH

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Figure 1: Effects of the gut microbiota on factors that contribute to the pathophysiology of NAFLD.
Figure 2: Photomicrographs of rat liver.
Figure 3: Inflammatory pathway induced by lipopolysaccharide (LPS).

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Acknowledgements

This work is supported in part by a grant from Science Foundation Ireland to the Alimentary Pharmabiotic Centre and by a scholarship to A. Abu-Shanab from the Egyptian Government.

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A. Abu-Shanab researched the data for the article. A. Abu-Shanab and E. M. M. Quigley contributed equally to discussing the content, writing the article and to review and/or editing of the manuscript before submission.

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Correspondence to Eamonn M. M. Quigley.

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Abu-Shanab, A., Quigley, E. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 7, 691–701 (2010). https://doi.org/10.1038/nrgastro.2010.172

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