Human metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA210341 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metagenome data from soil samples were collected at 0 to 10cm deep from 2 avocado orchards in Channybearup, Western Australia, in 2024. Amplicon sequence variant (ASV) tables were constructed based on the DADA2 pipeline with default parameters.
2025-06-15 | GSE298403 | GEO
Project description:Celiac disease (CeD) is an intestinal immune-mediated disorder caused by gluten ingestion in genetically predisposed subjects. CeD is characterized by villous atrophy, altered intestinal permeability, crypt hyperplasia and innate and adaptive immune response. This study aimed to develop and validate the use of intestinal organoids from celiac patients to study CeD. A repository of organoids from duodenum of non-celiac and celiac patients was generated and characterized accordingly to standard procedures. RNA-seq analysis was employed to study the global gene expression program of CeD (n=3) and non-CeD (n=3) organoids sets. While the three celiac derived organoids shared similar transcriptional signatures the NC samples set appeared more heterogeneous. We found 486 genes differentially expressed between the two groups. Of them, 299 genes were downregulated (FC<2; FDR<0.05) and 187 were upregulated in CeD (FC >2; FDR<0.05). We observed CeD organoids had significantly altered expression of genes associated with barrier function, innate immunity, and stem cell function.
2019-05-29 | GSE113492 | GEO
Project description:In vitro models of autoimmunity are constrained by an inability to culture affected epithelium alongside the complex tissue-resident immune microenvironment. Celiac disease (CeD) is an autoimmune disease where dietary gluten-derived peptides bind the MHC- II molecules HLA-DQ2 or -DQ8 to initiate immune-mediated duodenal mucosal injury. Here, we generated air-liquid interface (ALI) duodenal organoids from endoscopic biopsies that preserve epithelium alongside native mesenchyme and tissue-resident immune cells as a unit without requiring reconstitution. The ALI organoid immune diversity spanned T, B, plasma, NK and myeloid cells with extensive T and B cell receptor repertoires. HLA-DQ2.5-restricted gluten peptides selectively instigated epithelial destruction in HLA-DQ2.5-expressing CeD patient organoids, which was antagonized by MHC-II or NKG2C/D blockade. Gluten epitopes stimulated a CeD organoid network response in lymphoid and myeloid subsets alongside anti-TG2 autoantibody production. Functional studies in CeD organoids revealed IL-7 as a novel gluten-inducible pathogenic modulator which regulated CD8+ T cell-NKG2C/D expression and was necessary and sufficient for epithelial destruction. Further, endogenous IL-7 was markedly induced in patient biopsies from active CeD versus remission disease, predominantly in lamina propria mesenchyme. By preserving epithelium alongside diverse immune populations, this human in vitro CeD model recapitulates gluten-dependent pathology, facilitates mechanistic investigation, and establishes proof-of-principle for organoid modeling of autoimmunity.
2024-07-12 | GSE200075 | GEO
Project description:Celiac disease (CeD) is an immune-mediated chronic enteropathy caused by gluten exposure in HLA-DQ2 and/or -DQ8 positive individuals. The hallmarks of CeD include increased intraepithelial lymphocytes and villous atrophy. Clinically, a small subset of individuals with elevated serum tissue transglutaminase antibody (TTG) concentrations but unremarkable duodenal mucosa at initial endoscopy may progress to CeD over time. We hypothesize that these rare CeD precursor cases can allow us to interrogate histologic and molecular signatures to predict those who subsequently develop CeD, and to study the final cascade into overt lesions in CeD.
2025-08-06 | GSE273155 | GEO
Project description:The pathogenesis of celiac disease (CeD) remains incompletely understood. Traditional diagnostic techniques for CeD include serological testing and endoscopic examination; however, they have limitations. Therefore, there is a need to identify novel noninvasive biomarkers for CeD diagnosis. We analyzed duodenal and plasma samples from CeD patients by four-dimensional data-dependent acquisition (4D-DIA) proteomics. Differentially expressed proteins (DEPs) were identified for functional analysis and to propose blood biomarkers associated with CeD diagnosis. In duodenal and plasma samples, respectively, 897 and 140 DEPs were identified. Combining weighted gene co-expression network analysis(WGCNA) with the DEPs, five key proteins were identified across three machine learning methods. FGL2 and TXNDC5 were significantly elevated in the CeD group, while CHGA expression showed an increasing trend, but without statistical significance. The receiver operating characteristic curve results indicated an area under the curve (AUC) of 0.7711 for FGL2 and 0.6978 for TXNDC5, with a combined AUC of 0.8944. Exploratory analysis using Mfuzz and three machine learning methods identified four plasma proteins potentially associated with CeD pathological grading (Marsh classification): FABP, CPOX, BHMT, and PPP2CB. We conclude that FGL2 and TXNDC5 deserve exploration as potential sensitive, noninvasive diagnostic biomarkers for CeD.
2024-11-15 | PXD057692 | Pride
Project description:Coeliac Disease (CeD) is a chronic autoimmune disorder affecting 0.5-1% of the general population with a wide geographical distribution. Despite recent efforts to deeply phenotype gluten-specific immune activation at the single cell level, recent clinical studies targeting gluten degradation and other immune tolerance mechanisms have been unsuccessful. To this end, a deeper understanding of immune and non-immune cellular dynamics and interactions are required to characterize tissue-specific mechanisms responsible for CeD pathogenesis, repair, and resolution. Here, we assembled the most comprehensive scRNAseq dataset in Coeliac Disease to date, including 203,555 cells across 21 active CeD and 11 control duodenal samples. Compared to control duodenum, CeD was characterized by single cell differential changes in abundance, gene expression and cell-cell interactions across cellular compartments. In the immune compartments, CeD samples showed expected increases in plasma cell abundance and shifts toward type 1 effector biology (e.g., increase in cycling CD8pos, γδ T cells and IFNG transcriptional shifts) and Tfh-related biology (e.g., increases in IL21 signaling to effector T cells). In addition, activated myeloid subsets, including DC2 and monocytes, were increased in disease and were characterized by increased pro-inflammatory pathway expression, including IL-1β. Non-immune compartments showed increased stem/crypt and secretory enterocytes in CeD samples with a decrease in absorptive enterocytes, reflecting the villus atrophy and crypt hyperplasia hallmarks of CeD epithelial dysfunction. Accompanying the epithelial changes, distinct changes in stromal populations were identified, particularly with increases in abundance and transcriptional activity of NRG1 and SMOC2 fibroblasts. Cell-cell interaction analysis across multiple cellular compartments proposed a distinct increased role of fibroblasts to support the epithelial reprogramming of the increased stem/crypt epithelial fraction in CeD, mediated by myeloid derived IL-1β signal and lymphoid-derived IFN-γ. This dataset reveals a previously unknown role for T-myeloid-stromal-epithelial cell communication in CeD, highlighting key mechanisms of the tissue-level cellular dynamics in response to gluten ingestion.
2025-07-30 | GSE277276 | GEO
Project description:Pseudomonas putida KT2440 has received increasing attention as an important biocatalyst for the conversion of diverse carbon sources to multiple products, including the olefinic diacid, cis,cis-muconic acid (muconate). P. putida has been previously engineered to produce muconate from glucose; however, periplasmic oxidation of glucose causes substantial 2-ketogluconate accumulation, reducing product yield and selectivity. Deletion of the glucose dehydrogenase gene (gcd) prevents 2-ketogluconate accumulation, but dramatically slows growth and muconate production. In this work, we employed adaptive laboratory evolution to improve muconate production in strains incapable of producing 2-ketogluconate. Growth-based selection improved growth, but reduced muconate titer. A new muconate-responsive biosensor was therefore developed to enable muconate-based screening using fluorescence activated cell sorting. Sorted clones demonstrated both improved growth and muconate production. Mutations identified by whole genome resequencing of these isolates indicated that glucose metabolism may be dysregulated in strains lacking gcd. Using this information, we used targeted engineering to recapitulate improvements achieved by evolution. Deletion of the transcriptional repressor gene hexR improved strain growth and increased the muconate production rate, and the impact of this deletion was investigated using transcriptomics. The genes gntZ and gacS were also disrupted in several evolved clones, and deletion of these genes further improved strain growth and muconate production. Together, these targets provide a suite of modifications that improve glucose conversion to muconate by P. putida in the context of gcd deletion. Prior to this work, our engineered strain lacking gcd generated 7.0 g/L muconate at a productivity of 0.07 g/L/h and a 38% yield (mol/mol) in a fed-batch bioreactor. Here, the resulting strain with the deletion of hexR, gntZ, and gacS achieved 22.0 g/L at 0.21 g/L/h and a 35.6% yield (mol/mol) from glucose in similar conditions. These strategies enabled enhanced muconic acid production and may also improve production of other target molecules from glucose in P. putida.
2022-03-26 | GSE198795 | GEO
Project description:The common gamma chain (γc) is required for productive signaling by interleukin (IL)-15, IL-21 and IL-2, which are critically involved in immune activation and regulation. IL-21 and IL-15 are implicated in the pathogenesis of type-1 diabetes, graft-versus-host disease, and celiac disease (CeD), a gluten-mediated autoimmune-like enteropathy. Attempts to treat type-1 diabetes and graft-versus-host disease with biologics targeting one particular cytokine have failed. Both IL-15 and IL-21 have been suggested to drive activation of cytotoxic T cells (CTL) that are the effectors mediating tissue destruction in CeD and organ-specific autoimmune disorders. We show that the concomitant upregulation of IL-15 and IL-21 occurs only in full-blown CeD with villous atrophy. BNZ-2, a peptide that targets the γc, was able to block the cooperative IL-15/IL-21 mediated transcriptional activation of human tissue-resident intraepithelial CTL. Importantly, this inhibition was specific and did not interfere with IL-2 signaling, a cytokine with known immunoregulatory functions. Moreover, BNZ-2 blocked gluten-induced IFN-γ production in small intestinal organ cultures from CeD patients. These observations identify BNZ-2 as a therapeutic candidate for immune disorders in which IL-15 and IL-21 cooperate to induce CTL-mediated tissue damage.
2018-10-06 | GSE120904 | GEO