Integrated Gut/Liver-on-a-Chip platform as in vitro human model of non-alcoholic fatty liver disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE206417 | GEO | 2023/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:Non-alcoholic fatty liver disease (NAFLD) influence one of third population around the world. Until now, no effective treatments have been established due to the improper in vitro assays and experimental animal models. By co-culturing human gut and liver cell lines (CaCO2 and HepG2 cells, respectively) interconnected via the microfluidic closed medium circulation loop, we created a gut-liver-on-a-chip (iGLC) platform as an in vitro human model of the gut-liver axis (GLA) in initiation and progression of NAFLD.
2023-03-01 | GSE152091 | GEO
Project description:FLORINASH - The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD) EU FP7-HEALTH, project number 241913<br>Florinash examined the role on the gut microbiota in NAFLD. Metagenomic, proteomic, metabolomic and transcriptomic data were integrated to give provide a systems biology approach to disease-associated studies. Liver biopsies were obtained from patients undergoing bariatric surgery; one was used to diagnose NAFLD, the other was used to examine the host transcriptome in NAFLD. This dataset is part of the TransQST collection.
2018-03-15 | E-MTAB-4856 | biostudies-arrayexpress
Project description:Background & Aims: Non-alcoholic fatty liver disease (NALFLD)-associated changes in gut microbiota are important drivers of disease progression toward fibrosis. Therefore, reversing microbiota alterations could ameliorate NAFLD progression. Oat beta-glucan, a non-digestible polysaccharides, has shown promising therapeutic effects on hyperlipidemia associated with NAFLD, but its impact on gut microbiota and most importantly NAFLD fibrosis remains unknown. Methods: We performed detailed metabolic phenotyping including body composition, glucose tolerance, and lipid metabolism as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-induced model of NAFLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiota was modulated using broad-spectrum antibiotic (Abx) treatment. Results: Oat beta-glucan supplementation did not affect WSD-induced body weight gain, glucose intolerance, and the metabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened NAFLD inflammation, associated with significantly reduced monocyte-derived macrophages (MoMFs) infiltration, fibroinflammatory gene expression, and strongly reduced fibrosis development. Mechanistically, this protective effect was not mediated by changes in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon Abx treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in an expansion of protective taxa, including Ruminococcus, and Lactobacillus followed by reduced translocation of TLR ligands. Conclusions: Our findings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation and fibrosis development in diet-induced NAFLD. These results, along with its favorable dietary profile, suggest that it may be a cost-effective and well-tolerated approach to preventing NAFLD progression and should be assessed in clinical studies.
2024-01-01 | GSE246738 | GEO
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes. There are 12 samples in our study which belonged to 4 groups, and each group contains 3 different samples.
2015-01-23 | E-GEOD-65220 | biostudies-arrayexpress
Project description:Periodontitis increases the risk of non-alcoholic fatty liver disease (NAFLD). However, the precise mechanisms are unclear. Here, gut dysbiosis induced by orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, was implicated in the deterioration of NAFLD pathology. C57BL/6 mice were administered with the vehicle, P. gingivalis or Prevotella intermedia, with weaker periodontal pathogenicity, followed by feeding on a choline-deficient, high fat diet (CDAHFD60). CDAHFD60 feeding induced hepatic steatosis, and combined bacterial administration further aggravated NAFLD pathology with increased fibrosis. Liver gene expression analyses revealed that genes involved in the NAFLD pathology were perturbed with distinctive expression profiles induced by different bacteria. These differences may be due to quantitative and qualitative differences in the influx of gut bacterial products because the serum endotoxin level, gut microbiota composition, and serum metabolite profile caused by ingested P. intermedia and P. gingivalis were different. These findings provide insights into mechanisms linking periodontitis and NAFLD.
2021-11-03 | GSE136937 | GEO
Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.
2013-08-30 | E-GEOD-49542 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder and affects approximately one third of the general population.Recent studies have shown that long non-coding (lncRNA) plays critical roles in a myriad of biological processes and human diseases,Since the roles of lncRNA in NAFLD remain unknown,they were investigated in the study.Our findings indicate that the expression profiles of lncRNAs has changed in NAFLD as compared with normal liver, and may provide novel insight into the molecular mechanism underlying the disease and potential novel diagnostic or therapeutic targets for NAFLD. Microarray expression profiling of mRNAs and lncRNAs were conducted using RNA extracted from five NAFLD liver tissues and five normal liver samples.
2015-09-08 | E-GEOD-72756 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes.
2015-01-23 | GSE65220 | GEO
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes but their molecular pathogenesis is not fully elucidated. Global RNA sequencing of snap frozen liver tissue from 98 patients with biopsy-proven NAFLD was performed. Unsupervised hierarchical clustering well-distinguished NASH from NAFL, and NASH patients exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified multiple secreted proteins upregulated in NASH and/or advanced fibrosis
2021-05-31 | GSE167523 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, guar gum enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
2017-06-06 | GSE76087 | GEO