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Etiopathogenesis of NAFLD: Diet, Gut, and NASH

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Non-Alcoholic Fatty Liver Disease

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Abstract

In recent years, advancements in the knowledge of gut microbiota and its relationship with human pathophysiology led to the finding that gut microbiota is deeply implicated in the pathogenesis of liver steatosis and the progression to nonalcoholic steatohepatitis (NASH) and liver fibrosis.

Gut microbiota composition and gene expression are independently linked to NAFLD, as well as to many known risk factors for NAFLD such as obesity and insulin resistance. Furthermore, gut microbiota composition and function are deeply affected by diet and lifestyle. Diets rich in saturated fats, fructose, and cholesterol alter the gut microbiota and intestinal barrier function, favoring the onset and progression of NAFLD. Gut dysbiosis may affect several metabolic pathways, both through direct and indirect mechanisms (e.g., production of short-chain fatty acids, interaction with bile acid metabolism, modulation of intestine-derived hormones), eventually leading to increased hepatic de novo lipogenesis and alterations in glucose and lipid metabolism that perpetuate liver damage. Gut dysbiosis also leads to increased intestinal permeability and translocation of microorganisms and microbial products into the portal circulation (metabolic endotoxemia), triggering pro-inflammatory processes in the liver.

Available strategies to manipulate gut microbiota include the use of probiotic, prebiotic, or synbiotic supplements, or antibiotic treatment. Fecal microbiota transplantation has emerged as a further potential tool to modify gut microbiota composition. Novel therapeutic strategies include targeting the nuclear farnesoid X receptor (FXR), a transcription factor involved in the regulation of bile, glucose, and lipid metabolism, and the use of absorbents that bind to toxic metabolites in the gut.

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Authors and Affiliations

  1. Area Medicina Interna, Gastroenterologia e Oncologia Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Luca Miele, Marco Biolato, Francesca Mangiola, Antonio Liguori, Antonio Gasbarrini & Antonio Grieco

  2. Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy

    Luca Miele, Marco Biolato, Francesca Mangiola, Antonio Liguori, Antonio Gasbarrini & Antonio Grieco

  3. IRCCS Ospedale San Raffaele, Milan, Italy

    Caterina Conte

Authors
  1. Luca Miele
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  2. Marco Biolato
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  3. Caterina Conte
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  4. Francesca Mangiola
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  5. Antonio Liguori
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  6. Antonio Gasbarrini
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  7. Antonio Grieco
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Corresponding author

Correspondence to Luca Miele .

Editor information

Editors and Affiliations

  1. Department of Medical Sciences, Division of Gastroentrology and Hepatology, University of Turin, Turin, Italy

    Elisabetta Bugianesi

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Miele, L. et al. (2020). Etiopathogenesis of NAFLD: Diet, Gut, and NASH. In: Bugianesi, E. (eds) Non-Alcoholic Fatty Liver Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-95828-6_5

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  • DOI: https://doi.org/10.1007/978-3-319-95828-6_5

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  • Publisher Name: Springer, Cham

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