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The role of the gut microbiota in NAFLD

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TLDR
Improved methods of analysis of the gut microbiome, and greater understanding of interactions between dysbiosis, diet, environmental factors and their effects on the gut–liver axis should improve the treatment of this common liver disease and its associated disorders.
Abstract
NAFLD is now the most common cause of liver disease in Western countries. This Review explores the links between NAFLD, the metabolic syndrome, dysbiosis, poor diet and gut health. Animal studies in which the gut microbiota are manipulated, and observational studies in patients with NAFLD, have provided considerable evidence that dysbiosis contributes to the pathogenesis of NAFLD. Dysbiosis increases gut permeability to bacterial products and increases hepatic exposure to injurious substances that increase hepatic inflammation and fibrosis. Dysbiosis, combined with poor diet, also changes luminal metabolism of food substrates, such as increased production of certain short-chain fatty acids and alcohol, and depletion of choline. Changes to the microbiome can also cause dysmotility, gut inflammation and other immunological changes in the gut that might contribute to liver injury. Evidence also suggests that certain food components and lifestyle factors, which are known to influence the severity of NAFLD, do so at least in part by changing the gut microbiota. Improved methods of analysis of the gut microbiome, and greater understanding of interactions between dysbiosis, diet, environmental factors and their effects on the gut-liver axis should improve the treatment of this common liver disease and its associated disorders.

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Journal ArticleDOI

Mechanisms of NAFLD development and therapeutic strategies

TL;DR: Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression are discussed.
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MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease.

TL;DR: Experts reached consensus that NAFLD does not reflect current knowledge and metabolic (dysfunction) associated fatty liver disease "MAFLD" was suggested as a more appropriate overarching term and opens the door for efforts from the research community to update the nomenclature and sub-phenotype the disease in order to accelerate the translational path to new treatments.
Journal ArticleDOI

Lipotoxicity and the gut-liver axis in NASH pathogenesis

TL;DR: The initial mechanisms responsible for hepatocellular damage and inflammation, which derive from the toxic effects of excess lipids, are analyzed and accumulating data indicate that the total amount of triglycerides stored in hepatocytes is not the major determinant of lipotoxicity.
Journal ArticleDOI

Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease

TL;DR: The aim of this review is to give a comprehensive insight on the present researches and findings on the role of oxidative stress mechanisms in the pathogenesis and pathophysiology of NAFLD.
Journal ArticleDOI

Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders

TL;DR: Discrepant microbiome signatures across studies could be linked to the heterogeneity of geographical regions, ethnicity, population characteristics, microbiome sequencing tools, NAFLD diagnostic tools, disease spectrum, drug consumption and circadian rhythm.
References
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Journal ArticleDOI

An obesity-associated gut microbiome with increased capacity for energy harvest

TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
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Curtis Huttenhower, +253 more
- 14 Jun 2012 - 
TL;DR: The Human Microbiome Project Consortium reported the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome as discussed by the authors.
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Microbial ecology: Human gut microbes associated with obesity

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Journal ArticleDOI

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