Human intervention study with two doses of iron (as ferrous gluconate via intestinal perfusion) to study the effect on genome-wide gene expression in the small intestine, in order to obtain detailed information about intestinal transcriptomics in vivo.
Gene expression in human small intestinal mucosa in vivo is mediated by iron-induced oxidative stress.
Sex, Disease, Disease stage, Subject
View SamplesThe aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP48 (CIP104448), TIFN101 (CIP104450) or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.060.04 to 0.100.06, p=0.001), but was not significantly affected by the bacterial interventions. However, gene transcription pathway analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific effects on repair processes in the compromised intestine of healthy subjects.
The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial.
Sex, Specimen part, Treatment, Subject
View SamplesProbiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications.
Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways.
Specimen part
View SamplesSome commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-B-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli.
Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.
No sample metadata fields
View SamplesCortical tubers in patients with tuberous sclerosis complex (TSC) are associated with cognitive disability and intractable epilepsy. While these developmental malformations are believed to result from the effects of TSC1 or TSC2 Gene mutations, the molecular mechanisms leading to tuber formation during brain development as well as the onset of seizures remain largely unknown. We used the Affymetrix Gene Chip platform as a genome-wide strategy to define the Gene expression profile of cortical tubers resected during epilepsy surgery compared to histologically normal perituberal tissue (adjacent to the cortical tuber) from the same patients or autopsy control tissue.
Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors.
Specimen part, Disease, Subject
View SamplesAn increasing amount of evidence suggests that the small intestine may play an important role in the development of metabolic diseases, such as obesity and insulin resistance. The small intestine provides the first barrier between diet and the body. As a result, dysregulation of biological processes and secretion of signal molecules from the small intestine may be of importance in the regulation and dysregulation of whole body metabolic homeostasis. Changes in gene expression of genes involved in lipid metabolism, cell cycle and immune response may contribute to the aetiology of diet-induced obesity and insulin resistance. In the current study we present a detailed investigation on the effects a chow diet, low fat diet and high fat diet on gene expression along the proximal-to-distal axis of the murine small intestine. The reported results provide a knowledge base for upcoming studies on the role of the small intestine in the aetiology of diet-induced diseases.
Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.
Sex, Specimen part
View SamplesTo identify molecular subtypes of medulloblastoma we have profiled a series of 62 medulloblastoma tumors. Unsupervised hierarchical cluster analysis of these data identified 5 distinct molecular subtypes.
Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects.
Age, Specimen part
View SamplesGlomerular expression data from human kidney biopsy in African American subjects with glomerulopathies
Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects.
Age, Specimen part
View SamplesTubulointersitial expression data from human kidney biopsy in African American subjects with glomerulopathies
Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects.
Age, Specimen part
View Samples