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The effect of dietary fibre exposure on gene expression profiles in intestinal Caco-2 cells

ABSTRACT: Background: Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Dietary fibres have been descirbed to be beneficial for intestinal health. Therefore, in this study we explored the applicability of an in vitro model, namely human intestinal Caco-2 cells, to study the effect of dietary fibres on intestinal health. Transcriptomics was applied to obtain more insight into their mode of actions in the intestinal cells. Methods: Caco-2 cells were stimulated with 500 ug/ml dietary fibres and the maximal observed LPS contamination to serve as background control for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. To identify dietary fibre induced gene expression profiles in dietary fibre gene responses were compared to medium samples. Furthermore, to analyse differentiatlly affected pathways Ingenuite Pathway Analysis was employed. Results: Pathway analysis revealed a distinct separation between the dietary fibres. GOS and beta-glucan oat medium viscosity affected transcription of a lower amount of genes (gene cut-off p<0.05) and gen transcription changes suggest an increase in vesicle transport and altered cholesterol regulation. On the other hand, the other dietary fibres differentially regulated a larger numbers of genes (gene cut-off p<0.05) and all appeared related to immune responses. We observed an increase in intracellular and extracellular anti-bacterial pathways and production of cytokines specifically aimed at communication with the adaptive immune system. Conclusion: GOS and beta-glucan oat medium viscosity appeared to induce intestinal epithelial communication with the body, whereas the other dietary fibres appeared recognized as PAMP and induce epithelial cells to interact with the immune system.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99610 | GEO | 2022/05/30

REPOSITORIES: GEO

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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.

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The effect of dietary fibre exposure on gene expression profiles in intestinal Caco-2 cells

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