Despite accepted health benefits of dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic model, in which mice were colonized with a synthetic human gut microbiota, we elucidated the functional interactions between dietary fiber, the gut microbiota and the colonic mucus barrier, which serves as a primary defence against pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation promoted greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium, but only in the presence of a fiber-deprived microbiota that is pushed to degrade the mucus layer. Our work reveals intricate pathways linking diet, gut microbiome and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.
Specimen part
View SamplesNearly all colorectal cancers have dysregulated Wnt signalling, predominantly through the mutation of the Apc (Adenomatous Polyposis Coli) gene. Therefore it is of vital importance to elucidate the key Wnt target genes in intestinal cells in vivo. We have used a novel inducible cre-lox based murine system (designated ApcFlox) to investigate the consequences of perturbation of Wnt signalling following inactivation of Apc in vivo within 100% of the intestinal epithelium. We have employed microarray analysis at 3 time points within our ApcFlox system (Day 3 prior to the onset of phenotype, day 4 the establishment of the phenotype and day 5 gross phenotype of altered proliferation, differentiation and migration) and from adenomas arising in the ApcMin/+ background allowing us characterise Wnt/beta-catenin target genes based on their expression profiles during different stages of intestinal tumourigenesis. Furthermore, we have employed microarray analysis using livers from our ApcFlox system and have demonstrated that there is very little overlap in the Wnt target genes induced by Apc loss in the liver and the intestine. More importantly, we have been able to determine a novel set of putative Wnt/beta-catenin target genes which are upregulated at both early and late stages of tumourigenesis in the intestine and may represent novel therapeutic targets in colon cancer.
Hunk/Mak-v is a negative regulator of intestinal cell proliferation.
Specimen part
View SamplesBiomarkers of osteoarthritis (OA) that can accurately diagnose the disease at the earliest stage would significantly support efforts to develop treatments for prevention and early intervention. The different stages of disease progression are described by the complex pattern of transcriptional regulations. The dynamics in pattern alterations were monitored in each individual animal during the time-course of OA progression.
Blood Transcriptional Signatures for Disease Progression in a Rat Model of Osteoarthritis.
Treatment
View SamplesChronic opiate use produces molecular and cellular adaptations in the nervous system, leading to tolerance, physical dependence and addiction. Genome-wide comparison of morphine-induced changes in brain transcription of mouse strains with different opioid-related phenotypes provides an opportunity to discover the relationship between gene expression and behavioral response to the drug.
Morphine effects on striatal transcriptome in mice.
No sample metadata fields
View SamplesTo identify molecular effects of chronic drug treatment, heroin and methamphetamine treated animals were compared with saline treated animals at multiple time-points using microarray technology. Gene expression profile was assessed 14 h after the last dose of 1, 3, 6 or 12 days drug treatment and after 13, 15, 18 or 24 days of withdrawal.
Common transcriptional effects in the mouse striatum following chronic treatment with heroin and methamphetamine.
Specimen part, Compound
View SamplesChronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction.
Behavioral and transcriptional patterns of protracted opioid self-administration in mice.
Specimen part
View SamplesDifferences between groups of children with obesity and healthy controls.
Looking for new diagnostic tools and biomarkers of hypertension in obese pediatric patients.
Specimen part, Disease
View SamplesUsing whole-genome Affymetrix microarrays (HG-U133A), we characterized the transcriptome profile of cultured human macrophages stimulated for 4 h with interleukin 1 (IL-1) or interleukin 6 (IL-6). We found that, in distinction to liver cells, IL-1 is much more potent than IL-6 in modifying macrophage gene expression, although considerable heterogeneity in response of macrophages deriving from individual blood donors was observed. The obtained results permitted to identify a large number of cytokine-responsive genes. coding for proteins of unknown function that are now being studied in our laboratory. They may represent novel targets in the anti-inflammatory therapy.
Identification of interleukin-1 and interleukin-6-responsive genes in human monocyte-derived macrophages using microarrays.
No sample metadata fields
View SamplesIn summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile.
The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum.
Compound, Time
View SamplesMajor depression is a multidimensional disorder highly prevalent in modern society. Although several classes of antidepressants (ADs) are currently available to treat depression, the effectiveness of treatment is still limited, as many patients do not show full remission; thus, there is a need to find better patients directed therapeutic strategies. Neuroplastic changes in several brain regions, namely in the hippocampal dentate gyrus (DG), are amongst the best correlates of depression and of ADs actions. In this study the targets and molecular mediators of chronic stress and of four ADs from different pharmacological classes (fluoxetine, imipramine, tianeptine and agomelatine) were investigated in the DG.
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus.
Sex, Age, Specimen part
View Samples