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PROVIDER: PRJEB62828 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice
2018-09-17 | E-MTAB-6079 | ExpressionAtlas
Project description:Gut microbiota and gallstone formation - cohousing study
2020-01-10 | E-MTAB-8550 | ExpressionAtlas
Project description:BACKGROUND & AIMS: There is mounting evidence that microbes resident in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcoholic hepatitis (AH). However, mechanisms by which gut microbiota synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. METHODS: We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, and identified the metabolite trimethylamine (TMA) as a gut microbe-derived biomarker of AH. In subsequent studies, we treated mice with non-lethal mechanism-based bacterial choline TMA lyase inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. RESULTS: We show the gut microbial choline metabolite trimethylamine (TMA) is elevated in AH patients, which is correlated with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial choline TMA lyase activity protects mice from ethanol-induced liver injury. TMA lyase inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome community and host liver transcriptome. CONCLUSIONS: The microbial metabolite TMA is a biomarker of AH, and blocking TMA production from gut microbes can blunt ALD in mice.
2021-03-31 | GSE157681 | GEO
Project description:Gut microbiota dysbiosis characterizes systemic metabolic alteration, yet its causality is debated. To address this issue, we transplanted antibiotic-free conventional wild-type mice with either dysbiotic (“obese”) or eubiotic (“lean”) gut microbiota and fed them either a NC or a 72%HFD. We report that, on NC, obese gut microbiota transplantation reduces hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non-transplanted mice. Of note, this phenotype is blunted in conventional NOD2KO mice. By contrast, lean microbiota transplantation did not affect hepatic gluconeogenesis. In addition, obese microbiota transplantation changed both gut microbiota and microbiome of recipient mice. Interestingly, hepatic gluconeogenesis, PEPCK and G6Pase activity were reduced even once mice transplanted with the obese gut microbiota were fed a 72%HFD, together with reduced fed glycaemia and adiposity compared to non-transplanted mice. Notably, changes in gut microbiota and microbiome induced by the transplantation were still detectable on 72%HFD. Finally, we report that obese gut microbiota transplantation may impact on hepatic metabolism and even prevent HFD-increased hepatic gluconeogenesis. Our findings may provide a new vision of gut microbiota dysbiosis, useful for a better understanding of the aetiology of metabolic diseases. all livers are from NC-fed mice only.
2017-03-16 | GSE81318 | GEO
Project description:Non-alcoholic steatohepatitis (NASH), which is increasing in incidence due to the obesity epidemic, is a T-cell mediated, auto-aggressive condition that can result in progressive liver disease and hepatocellular carcinoma (HCC). The gut-liver axis contributes to NASH, yet mechanisms underlying metabolic T-cell activation and NASH-related fibrosis have largely remained elusive. We found that gastrointestinal B-cells are activated and increased in number in mouse/human NASH, allowing metabolic T-cell activation to induce NASH antigen- and microbiota-independently. Genetic/therapeutic depletion of B-cells systemically or of gastrointestinal B-cells specifically, prevented or reverted NASH and fibrosis. Secretion of immunoglobulins was essential for NASH and fibrosis development. IgA secretion was necessary for fibrosis-induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcRγ signaling-axis. Furthermore, clinical/molecular analyses from NASH-patients demonstrated IgA and activated FcRγ+ hepatic myeloid cells to correlate with the degree of liver-fibrosis. Thus, gastrointestinal B-cells and the IgA-FcRγ signaling-axis on hepatic myeloid cells represent potential therapeutic targets to treat NASH.
2023-11-22 | GSE190204 | GEO
Project description:Recent studies have revealed the pivotal role of gut microbiota in the precession of liver diseases including non-alcoholic steatohepatitis (NASH). Many natural herbs, such as Gynostemma pentaphyllum (GP), have been extensively used applied in the treatment prevention of NASH, while the bioactive components and underlying mechanism remain unclear. The aim of this study was to investigate whether the polysaccharides of GP (GPP) has the protective effect on of NASH and to explore the potential mechanism underlying these effects. To investigate the function high dose of GPP(HGPP) in the regulation of hepatic gene expression, C57BL/6 male mice were fed with methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH, and administered daily oral gavage of the sodium carboxymethylcellulose (CMC-Na) for model group, HGPP for experimental group, compared with normal control methionine-choline-sufficient (MCS) group.
2022-06-16 | GSE205974 | GEO
Project description:Here we report 16s rRNA data in gut microbiota of hepatocellular carcinoma (HCC) patients with HBV induced HCC (HBVC) and non-HBV induced HCC (NHBVC) compared with healthy volunteers. A total of 2047 operational taxonomic units (OTUs) were identified in the sequence data. Our data shows that the NHBVC patients harbor lower anti-inflammatory bacteria and more pro-inflammatory bacteria, while the HBVC patients harbor more anti-inflammatory bacteria.
2019-02-27 | GSE108847 | GEO
Project description:High-calorie diets lead hepatic steatosis and to the development of non-alcoholic fatty liver disease (NAFLD), which can evolve over many years into the inflammatory form non-alcoholic steatohepatits (NASH) posing a risk for the development of hepatocellular carcinoma (HCC). Due to the diet and the liver alteration, the axis between liver and gut is disturbed, resulting in gut microbiome alterations. Consequently, detecting these gut microbiome alterations repre-sents a promising strategy for early NASH and HCC detection. We analyzed medical parame-ters and the fecal metaproteome of 19 healthy controls, 32 NASH, and 29 HCC patients target-ing the discovery of diagnostic biomarkers. Here, NASH and HCC resulted in increased in-flammation status and shifts within the composition of the gut microbiome. Increased abun-dance of kielin/chordin, E3 ubiquitin ligase, and nucleophosmin 1 represented valuable fecal biomarkers indicating disease-related changes in the liver. Whereas a single biomarker failed to separate NASH and HCC, machine learning-based classification algorithms provided 0.86% accuracy in distinguishing between controls, NASH, and HCC. Conclusion: Fecal metaproteomics enables early detection of NASH and HCC by providing single biomarkers and ma-chine learning-based metaprotein panels.
2022-10-13 | PXD034175 | Pride
Project description:INSIG1 in NASH pathophysiology and in the hepatic wound-healing response
2020-12-11 | E-MTAB-9864 | ExpressionAtlas