Dataset Information

The Role of the Intestinal Microbiota in Nonalcoholic Steatohepatitis.

ABSTRACT: Nonalcoholic steatohepatitis (NASH) is a serious disease threatening public health, and its pathogenesis remains largely unclear. Recent scientific research has shown that intestinal microbiota and its metabolites have an important impact on the development of NASH. A balanced intestinal microbiota contributes to the maintenance of liver homeostasis, but when the intestinal microbiota is disequilibrated, it serves as a source of pathogens and molecules that lead to NASH. In this review, we mainly emphasize the key mechanisms by which the intestinal microbiota and its metabolites affect NASH. In addition, recent clinical trials and animal studies on the treatment of NASH by regulating the intestinal microbiota through prebiotics, probiotics, synbiotics and FMT have also been briefly elaborated. With the increasing understanding of interactions between the intestinal microbiota and liver, accurate and personalized detection and treatment methods for NASH are expected to be established.

SUBMITTER: Xiang H

PROVIDER: S-EPMC8861316 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The Role of the Intestinal Microbiota in Nonalcoholic Steatohepatitis.

Xiang Hui H Sun Dating D Liu Xin X She Zhi-Gang ZG Chen Yonghong Y

Frontiers in endocrinology 20220208

Nonalcoholic steatohepatitis (NASH) is a serious disease threatening public health, and its pathogenesis remains largely unclear. Recent scientific research has shown that intestinal microbiota and its metabolites have an important impact on the development of NASH. A balanced intestinal microbiota contributes to the maintenance of liver homeostasis, but when the intestinal microbiota is disequilibrated, it serves as a source of pathogens and molecules that lead to NASH. In this review, we mainl ...[more]

PMID: 35211093

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Project description:Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver that may progress to hepatic fibrosis and nonalcoholic steatohepatitis (NASH). Mechanisms underlying NAFLD and NASH are not yet fully understood. Dietary cholesterol was recently shown to be a risk factor for the development of NASH, suggesting a role for intestinal handling of cholesterol. One important regulator of cholesterol homeostasis is the sterol response element-binding protein-2 (SREBP-2) transcription factor. We tested the hypothesis that the overactivation of intestinal SREBP-2 increases the susceptibility to diet-induced NASH. A transgenic mouse model with intestine-specific overexpression of active SREBP-2 (ISR2 mice) driven by villin promoter was used. ISR2 mice and their wild-type littermates were fed a regular chow diet or a high-fat, high-cholesterol (HFHC) diet (15% fat, 1% cholesterol) for 15 wk. Results showed that HFHC feeding to ISR2 mice caused hepatic inflammation with increased levels of proinflammatory cytokines. Histological examination demonstrated extensive fibrosis after a HFHC diet associated with a perivascular as well as pericellular collagen deposits in ISR2 mice compared with wild-type littermates. The severe hepatic inflammation and advanced fibrosis in ISR2 mice was not associated with a difference in lipid accumulation in ISR2 mice compared with wild type littermates after HFHC feeding. These data indicate that overactivation of intestinal SREBP2 promotes diet-induced hepatic inflammation with features of human NASH resulting in rapid severe fibrosis and provide a novel link between regulatory processes of intestinal cholesterol and progression of fatty liver.NEW & NOTEWORTHY The current study highlights the role of overactivation of intestinal SREBP-2 transcription factor in the progression of hepatic fibrosis associated with diet-induced NASH. Mice with intestine-specific overexpression of SREBP-2 demonstrated more inflammation and severe fibrosis in the liver in response to 15 wk of being fed a high-cholesterol, high-fat diet as compared with their wild-type littermates. These data demonstrate a novel link between intestinal regulatory processes of cholesterol metabolism and the pathogenesis of fatty liver diseases.

Dataset Information

The Role of the Intestinal Microbiota in Nonalcoholic Steatohepatitis.

Publications

The Role of the Intestinal Microbiota in Nonalcoholic Steatohepatitis.

Similar Datasets

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