HAMSAB clinical T1D trial
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB45815 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR6212210.fastq.gz | Fastqsanger.gz | |||
| ERR6212220.fastq.gz | Fastqsanger.gz | |||
| ERR6212230.fastq.gz | Fastqsanger.gz | |||
| ERR6212240.fastq.gz | Fastqsanger.gz | |||
| ERR6212250.fastq.gz | Fastqsanger.gz |
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Project description:Increasing the consumption of dietary fibre has been proposed to alleviate the progression of non-communicable diseases such as obesity, type 2 diabetes and cardiovascular disease, yet the effect of dietary fibre on host physiology remains unclear. In this study, we performed a multiple diet feeding study in C57BL/6J mice to compare high fat and high fat modified with dietary fibre diets on host physiology and gut homeostasis by combining proteomic, metagenomic, metabolomic and glycomic techniques with correlation network analysis. We observed significant changes in physiology, liver proteome, gut microbiota and SCFA production in response to high fat diet. Dietary fibre modification did not reverse these changes but was associated with specific changes in the gut microbiota, liver proteome, SCFA production and colonic mucin glycosylation. Furthermore, correlation network analysis identified gut bacterial-glycan associations.
2021-09-08 | PXD014132 | Pride
Project description:HAMSAB supplement enhances SCFA production associated with microbiota and immune modulation in type 1 diabetes
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Project description:Precision microbiome modulation with discrete dietary fiber structures to direct SCFA production
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Project description:Background: The long-term high-fat, high-sugar diet exacerbates type 2 diabetes mellitus (T2DM)-related cognitive impairments. The negative impact of poor dietary patterns on brain development and neurological function may be related to gut microbiota disturbance. The role of phlorizin in mitigating glucose and lipid metabolism disorders is well documented. However, the protective effect of phlorizin on diabetes-related cognitive dysfunction is unclear. Therefore, the present study aimed to investigate the effect of dietary supplementation of phlorizin on high-fat and high-fructose diet (HFFD)-induced cognitive dysfunction and evaluate the crucial role of the microbiota-gut-brain axis. Results: Dietary supplementation of phlorizin for 14 weeks effectively prevented glucolipid metabolism disorder, spatial learning impairment, and memory impairment in HFFD mice. In addition, phlorizin improved the HFFD-induced decrease in synaptic plasticity, neuroinflammation, and excessive activation of microglia in the hippocampus. Transcriptomics analysis shows that the protective effect of phlorizin on cognitive impairment was associated with increased expression of neurotransmitters and synapse-related genes in the hippocampus. Phlorizin treatment alleviated colon microbiota disturbance, mainly manifested by an increase in gut microbiota diversity and the abundance of short-chain fatty acid (SCFA)-producing bacteria. The level of microbial metabolites, including SCFA, inosine 5'-monophosphate (IMP), and D (-)-beta-hydroxybutyric acid (BHB) were also significantly increased after phlorizin treatment. Moreover, integrating multiomics analysis observed tight connections between phlorizin-regulated genes, microbiota, and metabolites. Furthermore, removal of the gut microbiota via antibiotics treatment diminished the protective effect of phlorizin against HFFD-induced cognitive impairment, underscoring the critical role of the gut microbiota in mediating cognitive behavior. Importantly, supplementation with SCFA and BHB alone mimicked the regulatory effects of phlorizin on cognitive function. Conclusions: These results indicate that gut microbiota and their metabolites mediate the ameliorative effect of phlorizin on HFFD-induced cognitive impairment. Therefore, phlorizin can be used as an easy-to-implement nutritional therapy to prevent and alleviate metabolism-related neurodegenerative diseases by targeting the regulation of the microbiome-gut-brain axis.
2024-03-20 | GSE261887 | GEO
Project description:Barrier integrity is central to the maintenance of a healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic diseases such as food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD, we report that a fermentable fibre-rich diet alleviates AD severity and systemic allergen sensitization. The gut-skin axis underpins this phenomenon through SCFA, which strengthen skin barrier integrity by altering mitochondrial metabolism of epidermal keratinocytes. SCFA promote keratinocyte differentiation and the production of key structural lipids, resulting in enhanced barrier function. Our results demonstrate that dietary fibre and SCFA mitigate AD by improving barrier integrity, ultimately limiting early systemic allergen sensitization and development of disease.
2022-08-24 | GSE185640 | GEO
Project description:Background: Acetate, propionate, and butyrate are the main short-chain fatty acids (SCFA) produced in the colon as a result of microbial fermentation of dietary fibers. An increasing amount of evidence suggests that these SCFA have major health benefits. The composition of the microbiota is altered by dietary fat, and this is believed to impact SCFA production. Currently it is unknown whether host gene expression responses to SCFA are modulated by fat content of the diet. The aim of this study was to compare the changes in colonic gene expression profiles after acetate, propionate and butyrate infusions between a low fat and high fat diet. Methods: Male C57BL/6J mice were fed semi-synthetic low fat (10 energy%) or high fat (45 E%) diets starting 2 weeks before the SCFA treatment period. During treatment, mice received a rectal infusion of either an acetate, propionate, butyrate, or a saline (control) solution for 6 consecutive days, after which colon was subjected to gene expression profiling. Unsupervised visualization of the dataset was performed using Independent Principal Component Analysis. For each SCFA, similarities of its effects on a low fat and a high fat diet were assessed using Rank-Rank Hypergeometric Overlap. In addition, differentially expressed genes were identified, and gene set enrichment analysis was performed to determine functional implications of the regulated genes. Results: Taking into account the complete dataset, we observed that more variation in gene expression profiles was explained by fat content of the diet than by SCFA treatment. Gene expression responses to acetate and butyrate were similar on the low fat versus high fat diet, but were opposite for propionate. Functionally the expression changes reflected differential modulation of several metabolic processes; genes involved in oxidative phosphorylation, lipid catabolism, lipoprotein metabolism and cholesterol transport were suppressed by acetate and butyrate treatment, whereas propionate treatment resulted in changes in fatty acid and sterol biosynthesis, and in amino acid and carbohydrate metabolism. Conclusions: We demonstrated that dietary fat content impacts the colonic gene expression response to propionate, and to a lesser extent to acetate and butyrate. The study demonstrates that knowledge on diet composition is essential when studying effects of SCFAs on metabolism.
2022-06-01 | GSE48856 | GEO
Project description:The overall aim was to investigate the effects of low and high dose vitamin D supplementation on genome-wide gene expression and how this is modulated by genetic variation. We adopted a functional genomics approach to analyse study participants in the BEST-D clinical trial (placebo, low dose or high dose supplementation over a 12-month treatment period).
2018-04-21 | E-MTAB-6246 | biostudies-arrayexpress
Project description:Selenium (Se) is an essential nutrient for beef cattle health and commercial production. The molecular mechanisms responsible for physiological responses of the animal to dietary Se supplementation, however, have not been evaluated. Furthermore, the potential effect of two chemical forms (organic vs. inorganic) of Se on gene expression by Se-sufficient cattle has not been evaluated. Microarray analysis using the GeneChip Bovine Genome Array (Affymetrix, Inc., Santa Clara, CA) was conducted to determine if dietary Se supplementation in organic vs. inorganic form (OSe vs. ISe) differentially affects the liver gene expression profile in growing beef heifers. Sodium selenite (Prince Se Concentrate; Prince Agri Products, Inc., Quincy, IL) was used as the source of ISe form. Se-enriched yeast (Sel-Plex; Alltech, Inc., Nicholasville, KY) was used as the source of OSe form. Thirty Angus heifers (BW 393 ± 9 kg) were randomly assigned to 3 dietary treatments (n = 10): Control (Ctrl) group received no dietary Se supplementation; ISe treatment group daily received dietary supplementation of Se at 3 mg/animal from ISe source; OSe treatment group daily received dietary supplementation of Se at 3 mg/animal from OSe source. Six animals were randomly selected from each of 3 treatment groups for RNA extraction and microarray analysis.
2010-04-28 | E-GEOD-19696 | biostudies-arrayexpress
Project description:Purpose: Short chain fatty acids (SCFAs) produced by the gut microbiota have dual beneficial anti-inflammatory and anti-dysbiotic effects associated with the prevention of type 1 diabetes (T1D) in mice. We have conducted a single-arm trial of a dietary supplement (HAMSAB), to determine the effects of increasing SCFA delivery in adults with long-standing T1D. Particularly, we examined blood transcriptome in these patients using RNA-seq. Methods: Blood was collected from patients at baseline and after 6 weeks of HAMSAB supplementation. Whole blood was collected directly into Paxgene or Tempus tubes containing RNA stabilisers and extracted according to the manufacturer's protocol. Next-gene sequencing of patients’ whole blood transcriptome was performed by Genewiz using Illumina NovaSeq platform obtaining sequence depth of 50 million reads/sample. Results: Several signalling pathways including fatty acid oxidation were found to be regulated by HAMSAB
2022-01-26 | GSE176230 | GEO
Project description:The gut microbiome plays a critical role in enhancing the effectiveness of immune checkpoint blockade (ICB) therapy. Here, we demonstrate that oral supplementation with the prebiotics mannose slows tumor growth in immunocompetent mice in a manner dependent on the gut microbiota. This effect is associated with an increase in the abundance of Faecalibaculum. Mannose generates an immune-stimulatory tumor microenvironment (TME), characterized by a higher percentage of effector and memory CD8+ T cells, along with a notable immunoreactive gene expression signature. Crucially, mannose modulates the stemness program of CD8+ T cells and promotes the generation of progenitor exhausted CD8+ T cells (Tpex). Mechanistically, mannose enhances the production of the short-chain fatty acids (SCFA) propionate and butyrate by the gut microbiota. Administration of propionate and butyrate suppresses tumor progression and stimulates the expansion and differentiation of Tpex both in vivo and in vitro. Furthermore, mannose works synergistically with PD-1 blockade, resulting in tumor regression and enhanced differentiation of intratumoral Tpex into intermediate exhausted CD8+ T cells (Tex-int) and terminally exhausted CD8+ T cells (Tex-term). We also identified a gene signature related to mannose therapy that correlates with favorable responses to ICB across various cancers. Overall, our findings support the combination of mannose dietary supplementation with anti-PD-1 immunotherapy in treating ovarian cancer and suggest its potential for clinical application.
2025-03-17 | GSE285806 | GEO