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 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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Susceptibility to many human autoimmune diseases is under strong genetic control by class II human leukocyte antigen (HLA) allele combinations. These genes remain by far the greatest risk factors in ...the development of type 1 diabetes and celiac disease. Despite this, little is known about HLA influences on the composition of the human gut microbiome, a potential source of environmental influence on disease. Here, using a general population cohort from the All Babies in Southeast Sweden study, we report that genetic risk for developing type 1 diabetes autoimmunity is associated with distinct changes in the gut microbiome. Both the core microbiome and beta diversity differ with HLA risk group and genotype. In addition, protective HLA haplotypes are associated with bacterial genera Intestinibacter and Romboutsia. Thus, general population cohorts are valuable in identifying potential environmental triggers or protective factors for autoimmune diseases that may otherwise be masked by strong genetic control.
Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile ...environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth.
Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches.
Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61·1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R = 0·161; p = 0·029), while mode of delivery (C-section versus vaginal delivery) had an effect as well (R = 0·100; p = 0·044). Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth.
This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food ...antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development.
Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin.
It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several lines of evidence suggest a role for the gut microbiome in type 1 diabetes. Treating diabetes-prone rodents with probiotics or antibiotics prevents the development of the disorder. ...Diabetes-prone rodents also have a distinctly different gut microbiome compared with healthy rodents. Recent studies in children with a high genetic risk for type 1 diabetes demonstrate significant differences in the gut microbiome between children who develop autoimmunity for the disease and those who remain healthy. However, the differences in microbiome composition between autoimmune and healthy children are not consistent across all studies because of the strong environmental influences on microbiome composition, particularly diet and geography. Controlling confounding factors of microbiome composition uncovers bacterial associations with disease. For example, in a human cohort from a single Finnish city where geography is confined, a strong association between one dominant bacterial species,
Bacteroides dorei
, and type 1 diabetes was discovered (Davis-Richardson et al.
Front Microbiol
2014
;5:678). Beyond this, recent DNA methylation analyses suggest that a thorough epigenetic analysis of the gut microbiome may be warranted. These studies suggest a testable model whereby a diet high in fat and gluten and low in resistant starch may be the primary driver of gut dysbiosis. This dysbiosis may cause a lack of butyrate production by gut bacteria, which, in turn, leads to the development of a permeable gut followed by autoimmunity. The bacterial community responsible for these changes in butyrate production may vary around the world, but bacteria of the genus
Bacteroides
are thought to play a key role.
The Park Grass experiment (PGE) in the UK has been ongoing since 1856. Its purpose is to study the response of biological communities to the long-term treatments and associated changes in soil ...parameters, particularly soil pH. In this study, soil samples were collected across pH gradient (pH 3.6–7) and a range of fertilizers (nitrogen as ammonium sulfate, nitrogen as sodium nitrate, phosphorous) to evaluate the effects nutrients have on soil parameters and microbial community structure. Illumina 16S ribosomal RNA (rRNA) amplicon sequencing was used to determine the relative abundances and diversity of bacterial and archaeal taxa. Relationships between treatments, measured soil parameters, and microbial communities were evaluated. Clostridium, Bacteroides, Bradyrhizobium, Mycobacterium, Ruminococcus, Paenibacillus, and Rhodoplanes were the most abundant genera found at the PGE. The main soil parameter that determined microbial composition, diversity, and biomass in the PGE soil was pH. The most probable mechanism of the pH impact on microbial community may include mediation of nutrient availability in the soil. Addition of nitrogen to the PGE plots as ammonium sulfate decreases soil pH through increased nitrification, which causes buildup of soil carbon, and hence increases C/N ratio. Plant species richness and plant productivity did not reveal significant relationships with microbial diversity; however, plant species richness was positively correlated with soil microbial biomass. Plants responded to the nitrogen treatments with an increase in productivity and a decrease in the species richness.
Although bioinformatics is becoming increasingly central to research in the life sciences, bioinformatics skills and knowledge are not well integrated into undergraduate biology education. This ...curricular gap prevents biology students from harnessing the full potential of their education, limiting their career opportunities and slowing research innovation. To advance the integration of bioinformatics into life sciences education, a framework of core bioinformatics competencies is needed. To that end, we here report the results of a survey of biology faculty in the United States about teaching bioinformatics to undergraduate life scientists. Responses were received from 1,260 faculty representing institutions in all fifty states with a combined capacity to educate hundreds of thousands of students every year. Results indicate strong, widespread agreement that bioinformatics knowledge and skills are critical for undergraduate life scientists as well as considerable agreement about which skills are necessary. Perceptions of the importance of some skills varied with the respondent's degree of training, time since degree earned, and/or the Carnegie Classification of the respondent's institution. To assess which skills are currently being taught, we analyzed syllabi of courses with bioinformatics content submitted by survey respondents. Finally, we used the survey results, the analysis of the syllabi, and our collective research and teaching expertise to develop a set of bioinformatics core competencies for undergraduate biology students. These core competencies are intended to serve as a guide for institutions as they work to integrate bioinformatics into their life sciences curricula.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The analysis of amplified and sequenced 16S rRNA genes has become the most important single approach for microbial diversity studies. The new sequencing technologies allow for sequencing thousands of ...reads in a single run and a cost-effective option is split into a single run across many samples. However for this type of investigation the key question that needs to be answered is how many samples can be sequenced without biasing the results due to lack of sequence representativeness? In this work we demonstrated that the level of sequencing effort used for analyzing soil microbial communities biases the results and determines the most effective type of analysis for small and large datasets. Many simulations were performed with four independent pyrosequencing-generated 16S rRNA gene libraries from different environments. The analysis performed here illustrates the lack of resolution of OTU-based approaches for datasets with low sequence coverage. This analysis should be performed with at least 90% of sequence coverage. Diversity index values increase with sample size making normalization of the number of sequences in all samples crucial. An important finding of this study was the advantage of phylogenetic approaches for examining microbial communities with low sequence coverage. However, if the environments being compared were closely related, a deeper sequencing would be necessary to detect the variation in the microbial composition.
Shotgun metagenomics methods enable characterization of microbial communities in human microbiome and environmental samples. Assembly of metagenome sequences does not output whole genomes, so ...computational binning methods have been developed to cluster sequences into genome 'bins'. These methods exploit sequence composition, species abundance, or chromosome organization but cannot fully distinguish closely related species and strains. We present a binning method that incorporates bacterial DNA methylation signatures, which are detected using single-molecule real-time sequencing. Our method takes advantage of these endogenous epigenetic barcodes to resolve individual reads and assembled contigs into species- and strain-level bins. We validate our method using synthetic and real microbiome sequences. In addition to genome binning, we show that our method links plasmids and other mobile genetic elements to their host species in a real microbiome sample. Incorporation of DNA methylation information into shotgun metagenomics analyses will complement existing methods to enable more accurate sequence binning.
Abstract
Here, salivary microbiota and major histocompatibility complex (MHC) human leukocyte antigen (HLA) alleles were compared between 47 (12.6%) young adults with recent suicidal ideation (SI) ...and 325 (87.4%) controls without recent SI. Several bacterial taxa were correlated with SI after controlling for sleep issues, diet, and genetics. Four MHC class II alleles were protective for SI including DRB1*04, which was absent in every subject with SI while present in 21.7% of controls. Increased incidence of SI was observed with four other MHC class II alleles and two MHC class I alleles. Associations between these HLA alleles and salivary bacteria were also identified. Furthermore, rs10437629, previously associated with attempted suicide, was correlated here with SI and the absence of
Alloprevotella rava
, a producer of an organic acid known to promote brain energy homeostasis. Hence, microbial-genetic associations may be important players in the diathesis-stress model for suicidal behaviors.
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