Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model
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ABSTRACT:
PROVIDER: PRJEB54561 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR9919090_1.fastq.gz | Fastqsanger.gz | |||
| ERR9919090_2.fastq.gz | Fastqsanger.gz | |||
| ERR9919091_1.fastq.gz | Fastqsanger.gz | |||
| ERR9919091_2.fastq.gz | Fastqsanger.gz | |||
| ERR9919082_1.fastq.gz | Fastqsanger.gz |
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Project description: Not available
| S-EPMC9717514 | biostudies-literature
Project description:BACKGROUND & AIMS: Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. METHODS: Microarray was performed to identify differentially expressed genes in NASH. Quantitative real time PCR (qRT-PCR) was used to examine gene expression levels. Western blotting and immunofluorescence staining were employed to examine hemoglobin proteins. Flow cytometry was used to measure intracellular oxidative stress. RESULTS: Analysis of microarray gene expression data has revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopspies from NASH patients. Increased hemoglobin expression in NASH was validated by qRT-PCR. However, the expression of erythrocyte specific marker genes such as SPTA, SPTB, GYPA, GATA1, and ALAS2 did not change, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, induced a dose dependent increase in HBA1 expression in HepG2 cells. Intriguingly, forced hemoglobin expression suppressed oxidative stress. CONCLUSIONS: Oxidative stress upregulates hemoglobin expression in hepatocytes. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage. These findings suggest that hemoglobin is an inducible antioxidant in hepatocytes in response to increased oxidative stress as found in NASH livers. Twelve biopsy diagnosed NASH patients were included in this study. For control groups, total RNA from 5 different subjects were purchased from ADMET. These subjects are free from liver disease.
2010-10-20 | E-GEOD-24807 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that can progress from simple fatty liver disease to non-alcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism and excretion (ADME) of drugs. Differential gene expression between three clinically defined pathological groups; normal, steatosis and NASH was analyzed. The samples were diagnosed as normal, steatotic, NASH with fatty liver (NASH fatty) and NASH without fatty liver (NASH NF). Genome-wide mRNA levels in samples of human liver tissue were assayed with Affymetrix GeneChipM-. Human 1.0ST arrays
2011-07-12 | E-MEXP-3291 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. METHODS: Microarray was performed to identify differentially expressed genes in NASH. Quantitative real time PCR (qRT-PCR) was used to examine gene expression levels. Western blotting and immunofluorescence staining were employed to examine hemoglobin proteins. Flow cytometry was used to measure intracellular oxidative stress. RESULTS: Analysis of microarray gene expression data has revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopspies from NASH patients. Increased hemoglobin expression in NASH was validated by qRT-PCR. However, the expression of erythrocyte specific marker genes such as SPTA, SPTB, GYPA, GATA1, and ALAS2 did not change, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, induced a dose dependent increase in HBA1 expression in HepG2 cells. Intriguingly, forced hemoglobin expression suppressed oxidative stress. CONCLUSIONS: Oxidative stress upregulates hemoglobin expression in hepatocytes. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage. These findings suggest that hemoglobin is an inducible antioxidant in hepatocytes in response to increased oxidative stress as found in NASH livers.
2010-10-21 | GSE24807 | GEO
Project description: Not available
| S-EPMC7835418 | biostudies-literature
Project description:Neural circuits driving mammalian behaviors are highly plastic and modulated by internal and external factors, including the gut microbiome. We identify imidazole propionate (ImP), a microbial metabolite linked to metabolic disorders, as a key modulator of brain activity and behavior. Bacterially derived ImP enters the systemic circulation and brain, where it alters neuronal gene expression and activity in the hypothalamus without inducing overt neuroinflammation. Elevating systemic ImP promotes stress-related pathways and disrupts GABAergic/glutamatergic signaling in the hypothalamus before peripheral glucose dysregulation occurs. Similarly, colonization with the ImP-producing bacterium Eggerthella lenta elevates behavioral and molecular features of stress. In a mouse model of type 2 diabetes, the gut microbiome exhibits an enhanced ability to produce ImP, leading to elevated systemic levels that are associated with heightened stress responses. In humans, higher ImP associates with reduced hypothalamic reactivity to food cues, impaired stress-coping, and increased emotional eating, mirroring the causal links between ImP, hypothalamic activity, and stress-related behaviors in mice. Overall, these findings establish ImP as a notable microbial metabolite that links gut dysbiosis to altered hypothalamic function and stress in metabolic disease.
2025-06-26 | GSE300937 | GEO
Project description:Non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is a significant risk factor for hepatocellular carcinoma (HCC). However, a preclinical model of progressive NAFLD/NASH is largely lacking. Here, we report that mice with hepatocyte-specific deletion of Tid1, encoding a mitochondrial cochaperone, tended to develop NASH-dependent HCC. Mice with hepatic Tid1 deficiency showed impairing mitochondrial function and causing fatty acid metabolic dysregulation; meanwhile, sequentially developed fatty liver, NASH, and cirrhosis/HCC in a diethylnitrosamine (DEN) induced oxidative environment. The pathological signatures of human NASH, including cholesterol accumulation and activation of inflammatory and apoptotic signaling pathways, are also present in these mice. Clinically, low Tid1 expression was associated with unfavorable prognosis in patients with HCC. Empirically, hepatic Tid1 deficiency directly disrupts entire mitochondria that play a key role in the NASH-dependent HCC development. Overall, we established a new mouse model that develops NASH-dependent HCC and provides a promising approach to improve the treatment.
2022-06-02 | E-MTAB-9973 | biostudies-arrayexpress
Project description:Cervicovaginal microbiome dysbiosis is associated with increased prevalence and incidence of sexually transmitted infections including HIV. We compared the cervicovaginal proteome as characterised by mass-spectrometry of four groups of African female sex workers (total N=50) grouped by microbiome composition as characterised by 16S rDNA microarray. Group 1 had a Lactobacillus crispatus-dominated microbiome, group 2 a L. iners-dominated microbiome, and groups 3 and 4 had a microbiome containing multiple genera of anaerobic bacteria, with group 3 representing transition to or from dysbiosis and group 4 full dysbiosis. 82 human proteins were differentially abundant among the groups, either showing an increasing or decreasing trend from microbiome groups 1 to 4. Proteins that increased included proteasome subunits and other proteins involved in catabolic metabolism, actin organising proteins and proteins involved in the immune response. Proteins that decreased included antiproteases, keratins, and cornified envelope proteins. We also compared the abundance of pre-defined proteins of interest among microbiome groups: markers of cell type, inflammation, and cell death, and mucins. The dysbiotic groups had increased abundance of proteins unique to lymphocytes and macrophages, pro-inflammatory cytokines, cell death markers, and MUC5B. We conclude that the cervicovaginal human proteome is associated with the cervicovaginal microbiome in a dose-response manner. The changes are likely caused by a pro-inflammatory influx of immune cells and an increase of cell death in dysbiosis. Dysbiosis-associated immune activation, breaches in epithelial integrity, altered mucin balance, and altered protease-antiprotease balance may all contribute to the increased risk of HIV transmission when cervicovaginal dysbiosis is present.
2015-09-25 | PXD001435 | Pride
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.
2013-04-02 | E-GEOD-37031 | biostudies-arrayexpress