Taxonomic identity provides information regarding the microbial communities, but falls short of expressing the functions present in the environment. all functions identified in cases and controls.(XLSX) pone.0025792.s005.xlsx (367K) GUID:?F1E5C3D8-F369-436B-B92F-3A81E554C46B Supporting Dataset S3: The results of 16S rRNA mining from the metagenomic data. All six levels of taxonomic discrimination are listed with the level of statistical difference between cases and controls for each taxon. Data are listed as a % of all 16S rRNA reads mined from the metagenomic data.(XLSX) pone.0025792.s006.xlsx (244K) GUID:?A2BC2516-0683-41E7-93FA-0BFBE53BE257 Supporting Dataset S4: ARRY-380 (Irbinitinib) The genera that differ statistically between cases and controls at a p-values ARRY-380 (Irbinitinib) of 0.01 or less. Data are listed as a % of all 16S rRNA reads mined from the metagenomic data.(XLSX) pone.0025792.s007.xlsx (55K) GUID:?0702A8E2-304C-4ED0-9FB2-075F4EDC6CD5 Abstract Recent studies have suggested a bacterial role in the development of autoimmune disorders including type 1 diabetes (T1D). Over 30 billion nucleotide bases of Illumina shotgun metagenomic data were analyzed from stool samples collected from four pairs of matched T1D case-control subjects collected at the time of the development of T1D associated autoimmunity (i.e., autoantibodies). From these, approximately one million open reading frames were predicted and compared to the SEED protein database. Of the 3,849 functions identified in these samples, 144 and 797 were statistically more prevalent in cases and controls, respectively. Genes involved in carbohydrate metabolism, adhesions, motility, phages, prophages, sulfur metabolism, and stress responses were more abundant in cases while genes with roles in DNA and protein metabolism, aerobic respiration, and amino acid synthesis were more common ARRY-380 (Irbinitinib) in controls. These data suggest that increased adhesion and flagella synthesis in autoimmune subjects may be involved in triggering a T1D associated autoimmune response. Extensive differences in metabolic potential indicate that autoimmune subjects have a functionally aberrant microbiome. Mining 16S rRNA data from these datasets showed a higher proportion of butyrate-producing and mucin-degrading bacteria in controls compared to cases, while those bacteria that produce short chain fatty acids other than butyrate were higher in cases. Thus, a key rate-limiting step in butyrate synthesis is more abundant in controls. These data suggest that a consortium of lactate- and butyrate-producing bacteria in a healthy gut induce a sufficient amount of mucin synthesis to maintain gut integrity. In contrast, non-butyrate-producing lactate-utilizing bacteria prevent optimal mucin synthesis, as identified in autoimmune subjects. Introduction As the incidence of type 1 diabetes (T1D) in developed countries has been increasing at a rate far beyond the rate of population growth, environmental factors have been considered as likely candidates responsible for this change in disease incidence in recent decades [1]C[3]. Of those factors, the gut microbiota have come under recent interest; supported in part by observations in both non-obese diabetic (NOD) mice and BioBreeding Diabetes Prone (BB-DP) rats where antibiotic use prevents the onset of diabetes [4], [5]. Initial studies found that NOD mice raised in germ-free environments would spontaneously develop diabetes [6], while a recent study suggested that rather than being diminished under germ-free conditions, the development of T1D can be prevented through modulation of the intestinal microbiota [7]. Likewise, both the NOD mouse and BB-DP rats treated with Freund’s adjuvants or strains delayed or decreased incidence of diabetes [8]C[16]. With respect Rabbit polyclonal to Caspase 1 to mechanisms of action, the gut microbiome of NOD mice lacking an adaptor for multiple innate immune receptors responsible for recognizing microbial stimuli correlates with disease onset, revealing a relationship between gut microbiota and the immune system [15]. To explore specific differences in the microbial communities responsible for T1D modulation, 16S rRNA amplicons were sequenced from BB-DP and BioBreeding Diabetes Resistant (BB-DR) rat stool samples collected around the time of diabetes onset [17]. This analysis revealed bacteria genera whose members were either ARRY-380 (Irbinitinib) positively or negatively correlated with diabetes. and were ARRY-380 (Irbinitinib) more abundant in BB-DR rats while and were more abundant in BB-DP rats. Both and are well known to have members with probiotic characteristics. In humans, inflammatory bowel diseases (IBD) such as Crohn’s and ulcerative colitis, are thought to be autoimmune and have been correlated with a depletion of commensal bacteria from the phyla Firmicutes and Bacteroidetes [18]. Fecal microbial communities in identical twins with Crohn’s disease show a decrease in diversity when compared.
