Dataset Information

The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression.

SUBMITTER: Yu J

PROVIDER: S-EPMC4876215 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background.

Yu Jinsheng J Marsh Sharon S Hu Junbo J Feng Wenke W Wu Chaodong C

Gastroenterology research and practice 20160509

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cel ...[more]

PMID: 27247565

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Project description:Aim: To investigate the intestinal flora of nonalcoholic fatty liver disease (NAFLD) in Chinese children and adolescents using metagenomic approach. Methods: All participants underwent magnetic resonance spectroscopy (MRS) to quantify liver fat content. Hepatic steatosis was defined as MRS proton density fat fraction (MRS-PDFF) >5%. A total of 58 children and adolescents were enrolled in this study, including 25 obese NAFLD patients, 18 obese non-NAFLD children, and 15 healthy children. Stool samples were collected and analyzed with metagenomics. We used Shannon index to reflect the alpha diversities of gut microbiota. Wilcoxon rank sum test and Kruskal-Wallis test were performed to evaluate alpha diversities between groups. At last, the differences of gut microbiota composition and functional annotations between obese with and without NAFLD and healthy children were assessed by Kruskal-Wallis test. Results: Significant differences in gut microbiota composition and functional annotations among three groups of children and adolescents have been observed. Deep sequencing of gut microbiota revealed high abundance of phylum Proteobacteria (Gammaproteobacteria) in obese NAFLD patients, comparing with the control group. Overall, obese children without NAFLD had less abundant Helicobacter and Helicobacter pylori. Compared to the control group, in obese children with NAFLD, the abundance of Bacteroidetes (Alistipes) were significantly reduced. Faecalibacterium prausnitzii was the only species representing a difference between obese children with and without NAFLD. There were not significant differences in terms of alpha diversity among three groups. Functional annotations demonstrated that several pathways were differentially enriched between groups, including metabolism of other amino acids, replication and repair, folding, sorting, degradation, and glycan biosynthesis and metabolism. Conclusion: Significantly differences are observed in gut microbiota composition and functional annotations between obese children with and without NAFLD in comparison to the healthy children group. The characteristic of gut microbiota in this study may contribute to a further understanding the gut-liver axis of pediatric NAFLD in China.

Dataset Information

The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background.

Publications

The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background.

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