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Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data is available on fungal dysbiosis in the children at the risk of type 1 diabetes (T1D). We hypothesized that the co-occurrence of fungal and bacterial dysbiosis contributes to the intestinal inflammation and autoimmune destruction of insulin-producing beta-cells in T1D. Fecal and blood samples were collected from 26 children tested positive for at least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) and matched autoantibody-negative children with HLA-conferred susceptibility to T1D (matched for HLA-DQB1 haplotype, age, gender and early childhood nutrition). Bacterial 16S and fungal ITS2 sequencing, and analyses of the markers of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). Nine autoantibody positive children were diagnosed with T1D, whereas none of the autoantibody negative children developed T1D during the follow-up. Fungal dysbiosis, characterized by high abundance of fecal Saccharomyces and Candida, was found in the progressors, i.e., children with beta-cell autoimmunity who during the follow-up progressed to clinical T1D. These children showed also bacterial dysbiosis, i.e., increased Bacteroidales and Clostridiales ratio, which was, however, found also in the non-progressors, and is thus a common nominator in the children with beta-cell autoimmunity. Furthermore, the progressors showed markers of intestinal inflammation detected as increased levels of fecal HBD2 and ASCA IgG to fungal antigens. We conclude that the fungal and bacterial dysbiosis, and intestinal inflammation are associated with the development of T1D in children with beta-cell autoimmunity.
Pubmed ID: 32265922 RIS Download
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A fungal rDNA internal transcribed spacer (ITS) sequence database (although additional genes and genetic markers are also welcome) to facilitate identification of environmental samples of fungal DNA. Additional important features include user annotation of INSD sequences to add metadata on, e.g., locality, habitat, soil, climate, and interacting taxa. The user can furthermore annotate INSD sequences with additional species identifications that will appear in the results of any analyses done. UNITE focuses on high-quality ITS sequences generated from fruiting bodies collected and identified by experts and deposited in public herbaria. In addition, it also holds all fungal ITS sequences in the International Nucleotide Sequence Databases (INSD: NCBI, EMBL, DDBJ). Both sets of sequences may be used in any analyses carried out. UNITE is accompanied by a project management system called PlutoF, where users can store field data, document the sequencing lab procedures, manage sequences, and make analyses. PlutoF intends to make it possible for taxonomists, ecologists, and biogeographers to use a common platform for data storage, handling, and analyses, with the intent of facilitating an integration of these disciplines. A user can have an unlimited number of projects but still make analyses across any project data available to him.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 23,2023.Software package for comparison and analysis of microbial communities, primarily based on high-throughput amplicon sequencing data, but also supporting analysis of other types of data. QIMME analyzes and transforms raw sequencing data generated on Illumina or other platforms to publication quality graphics and statistics.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsOrdination methods, diversity analysis and other functions for community and vegetation ecologists.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented Setember 8, 2016. A suite of tools for the comparison of microbial communities using phylogenetic information. It takes as input a single phylogenetic tree that contains sequences derived from at least two different environmental samples and a file describing which sequences came from which sample.
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