Dataset Information

Rutin and Its Combination With Inulin Attenuate Gut Dysbiosis, the Inflammatory Status and Endoplasmic Reticulum Stress in Paneth Cells of Obese Mice Induced by High-Fat Diet.

ABSTRACT: Gut dysbiosis induced by high fat diet (HF) or obesity is a predisposing factor to develop diverse inflammatory diseases. Polyphenols and fibers, often eaten together, have been reported to have prebiotic actions, but their health promoting benefits still need to be further characterized and defined. This study attempted to understand how polyphenol rutin and polysaccharide inulin influence intestinal health in mouse model fed a HF (60 kcal%) diet. A total of 48 C57BL/6J mice were divided into four groups fed with a low fat (10% kcal%) control diet (LC), a high fat control diet (HC), a high-fat diet supplemented with rutin (HR), or a high-fat diet supplemented rutin and inulin (HRI) for 20 weeks. Rutin supplementation reduced the HF diet-induced increase of Firmicutes/Bacteroidetes (F/B) ratio, Deferribacteraceae population and plasma lipopolysaccharide (LPS) (p < 0.05); ameliorated inflammation as indicated by the decreased circulating inflammatory cytokines (p < 0.05) and the reduced expressions of intestinal inflammatory mediators (p < 0.05); and attenuated the endoplasmic reticulum (ER) stress in Paneth cells as indicated by the decreased expressions of the ER markers (p < 0.05). Compared to the rutin supplementation alone, the co-administration of rutin with inulin improved the utilization of rutin as indicated by its decreased excretion, suppressed a number of harmful bacteria including Deferribacteraceae and Desulfovibrionaceae (p < 0.05), and further reduced the expression of the key inflammatory cytokine TNF-? and increased the production of butyrate, despite the supplementation of inulin reversed the decrease of body weight induced by rutin supplementation due to an increased food intake. Taken together, our data demonstrated that rutin supplementation ameliorated the inflammatory status and ER stress in Paneth cells under a HF-induced obese state, and its co-administration with inulin further mitigated the inflammatory status, indicating the potential to combine polyphenol rutin and the polysaccharide inulin as a dietary strategy to ameliorate gut dysbiosis, to improve inflammatory status and thereby to reduce medical disorders associated with HF-induced obesity.

SUBMITTER: Guo X

PROVIDER: S-EPMC6230659 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Rutin and Its Combination With Inulin Attenuate Gut Dysbiosis, the Inflammatory Status and Endoplasmic Reticulum Stress in Paneth Cells of Obese Mice Induced by High-Fat Diet.

Guo Xiulan X Tang Renyong R Yang Shiyong S Lu Yurong Y Luo Jing J Liu Zhenhua Z

Frontiers in microbiology 20181105

Gut dysbiosis induced by high fat diet (HF) or obesity is a predisposing factor to develop diverse inflammatory diseases. Polyphenols and fibers, often eaten together, have been reported to have prebiotic actions, but their health promoting benefits still need to be further characterized and defined. This study attempted to understand how polyphenol rutin and polysaccharide inulin influence intestinal health in mouse model fed a HF (60 kcal%) diet. A total of 48 C57BL/6J mice were divided into f ...[more]

PMID: 30455677

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Project description:The aim of the study was to examine whether there was excessive endoplasmic reticulum stress (ERs) in the islets of high?fat diet (HFD)?induced obese mice, as well as the effects of ERs on ??cell function. Male C57BL/6J mice were fed a HFD for 16 weeks. Pancreatic ??cell function was evaluated using intraperitoneal glucose tolerance and insulin release tests, and via electron microscopy. The expression of activating transcription factor 6 (ATF6) and phosphorylated (p)?eukaryotic initiation factor 2? (eIF2?) were detected via immunofluorescence staining to determine whether exposure to a HFD induced ERs in pancreatic islets. In vitro, ERs was induced by palmitate (PA) in INS?1 cells, and the protein expression of ATF6, and mRNA expression of ATF6 and insulin were examined via western blot and quantitative PCR (qPCR) analyses, respectively. The nuclear localization of ATF6 was examined by immunofluorescence. Finally, small interfering (si)RNA was used to downregulate ATF6 expression in INS?1 cells to further determine whether ATF6 mediated the ERs?induced impairment of insulin gene transcription. After 16 weeks of induction, the obese mice showed impaired glucose tolerance, insulin resistance and hyperinsulinemia. Immunohistochemistry staining showed increased p?eIF2? and ATF6 expression in pancreatic islets in the obesity group compared with the normal group. Electron microscopy indicated that the microstructures and secretory functions of ??cells were impaired. After 24 h of incubation, ATF mRNA and protein expression in the PA group was significantly higher compared with the control group. However, the insulin mRNA expression in the PA group was significantly decreased. Furthermore, qPCR showed that the insulin mRNA expression was significantly increased 24 h after PA treatment in cells transfected with ATF6?siRNA compared with the negative control group. The present suggested shows that ERs?induced activation of ATF6 may play an important role in the development of ??cell dysfunction in obese mice.

Project description:BackgroundPaneth cell dysfunction has been implicated in a subset of Crohn's disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients.MethodsPediatric CD (n = 44) and non-IBD (n = 62) patients aged 4 to 18 were recruited prior to routine endoscopic biopsy. Ileal mucosal samples were analyzed for Paneth cell phenotypes, mucosal microbiome composition, and RNA transcriptome.ResultsThe prevalence of abnormal Paneth cells was higher in pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal Paneth cells showed significant changes in their ileal mucosal microbiome, highlighted by reduced protective microbes and enriched proinflammatory microbes. Ileal transcriptome profiles showed reduced transcripts for genes that control oxidative phosphorylation in CD patients with abnormal Paneth cells. These transcriptional changes in turn were correlated with specific microbiome alterations. In non-IBD patients, a subset contained abnormal Paneth cells. However, this subset was not associated with alterations in the microbiome or host transcriptome.ConclusionPaneth cell abnormalities in human subjects are associated with mucosal dysbiosis in the context of CD, and these changes are associated with alterations in oxidative phosphorylation, potentially in a feedback loop.FundingThe research was funded by Helmsley Charitable Trust (to T.S. Stappenbeck, R.J. Xavier, and D.P.B. McGovern), Crohn's and Colitis Foundation of America (to N.H. Salzman, T.S. Stappenbeck, R.J. Xavier, and C. Huttenhower), and Doris Duke Charitable Foundation grant 2014103 (to T.C. Liu).

Dataset Information

Rutin and Its Combination With Inulin Attenuate Gut Dysbiosis, the Inflammatory Status and Endoplasmic Reticulum Stress in Paneth Cells of Obese Mice Induced by High-Fat Diet.

Publications

Rutin and Its Combination With Inulin Attenuate Gut Dysbiosis, the Inflammatory Status and Endoplasmic Reticulum Stress in Paneth Cells of Obese Mice Induced by High-Fat Diet.

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