The dynamics of a family’s gut microbiota reveal variations on a theme

Abstract Background It is clear that the structure and function of the human microbiota has significant impact on maintenance of health and yet the factors that give rise to an adult microbiota are poorly understood. A combination of genetics, diet, environment, and life history are all thought to impact the development of the gut microbiome. Here we study a chronosequence of the gut microbiota found in eight individuals from a family consisting of two parents and six children ranging in age from two months to ten years old. Results Using 16S rRNA gene and metagenomic shotgun sequence data, it was possible to distinguish the family from a cohort of normal individuals living in the same geographic region and to differentiate each family member. Interestingly, there was a significant core membership to the family members’ microbiota where the abundance of this core accounted for the differences between individuals. It was clear that the introduction of solids represents a significant transition in the development of a mature microbiota. This transition was associated with increased diversity, decreased stability, and the colonization of significant abundances of Bacteroidetes and Clostridiales. Although the children and mother shared essentially the identical diet and environment, the children’s microbiotas were not significantly more similar to their mother than they were to their father. Conclusions This analysis underscores the complex interactions that give rise to a personalized microbiota and suggests the value of studying families as a surrogate for longitudinal studies.http://deepblue.lib.umich.edu/bitstream/2027.42/109502/1/40168_2014_Article_54.pd

The Human Microbiome and Recurrent Abdominal Pain in Children

This project explores the nature of the human intestinal microbiome in healthy children and children with recurrent abdominal pain. The overall goal is to obtain a robust knowledge base of the intestinal microbiome in children without evidence of pain or gastrointestinal disease and in those with recurrent abdominal pain (functional abdominal pain (FAP) and FAP associated with changes in bowel habits, i.e., irritable bowel syndrome or IBS). Specific aims include: 1. Characterize the composition of the gut microbiome in healthy children by DNA sequencing. 2. Determine the presence of disease-specific organism signatures of variable gut microbiomes in children with recurrent abdominal pain. 3. Perform functional gut metagenomics by evaluation of whole community gene expression profiles and discovery of disease-specific pathway signatures. Multiple strategies have been deployed to navigate and understand the nature of the intestinal microbiome in childhood. These strategies included 454 pyrosequencing-based strategies to sequence 16S rRNA genes and understand the detailed composition of microbes in healthy and disease groups. Microarray-based hybridization with the PhyloChip and quantitative real-time PCR (qPCR) probes were applied as complementary strategies to gain an understanding of the intestinal microbiome from various perspectives. Data collected and analyzed during the HMP UH2 Demo project, from a set of healthy and IBS children (7-12 yo) may enable the identification of core microbiomes in children, in addition to variable components that may distinguish healthy from diseased pediatric states. Twenty-two children with IBS and twenty-two healthy children were enrolled and analyzed in the UH2 phase of this study. The planned enrollment targets for the UH2/3 phases include 50 healthy children, 50 children with FAP and 50 children with IBS (minimum of 3 time points per child). We are currently analyzing the dataset for the presence of disease-specific signatures in the human microbiome, and correlating these microbial signatures with pediatric health or IBS disease status in addition to IBS subtype (e.g., diarrhea-vs constipation-predominant). In the next phase, whole genome shotgun sequencing and metatranscriptomics will be performed with a subset of children in each group. This study explores the nature of core and variable human microbiome in pre-adolescent healthy children and children with IBS. 
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Improved Cauchy radius for scalar and matrix polynomials

We improve the Cauchy radius of both scalar and matrix polynomials, which is an upper bound on the moduli of the zeros and eigenvalues, respectively, by using appropriate polynomial multipliers.Comment: 12 page

The Human Microbiome Project: A Community Resource for the Healthy Human Microbiome

The Human Microbiome Project (HMP) [1],[2] is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the “other genome" of microbes carried in and on the human body [3],[4]. Microbial ecologists, realizing that >99% of environmental microbes could not be easily cultured, developed approaches to study microorganisms in situ [5], primarily by sequencing the 16S ribosomal RNA gene (16S) as a phylogenetic and taxonomic marker to identify members of microbial communities [6]. The need to develop corresponding new methods for culture-independent studies [7],[8] in turn precipitated a sea change in the study of microbes and human health, inspiring the new term “metagenomics" [9] both to describe a technological approach—sequencing and analysis of the genes from whole communities rather than from individual genomes—and to emphasize that microbes function within communities rather than as individual species. This shift from a focus on individual organisms to microbial interactions [10] culminated in a National Academy of Science report [11], which outlined challenges and promises for metagenomics as a way of understanding the foundational role of microbial communities both in the environment and in human health.National Institutes of Health (U.S.) (grant U54HG004969)National Institutes of Health (U.S.) (grant U54HG004973)National Institutes of Health (U.S.) (grant U54AI084844)National Institutes of Health (U.S.) (grant U01HG004866)National Institutes of Health (U.S.) (grant R01HG005969)National Institutes of Health (U.S.) (grant R01HG004872)United States. Army Research Office (grant W911NF-11-1-0473)National Science Foundation (U.S.) (NSF DBI-1053486)Howard Hughes Medical Institute (Early Career Scientist

A Full-Genomic Sequence-Verified Protein-Coding Gene Collection for Francisella tularensis

The rapid development of new technologies for the high throughput (HT) study of proteins has increased the demand for comprehensive plasmid clone resources that support protein expression. These clones must be full-length, sequence-verified and in a flexible format. The generation of these resources requires automated pipelines supported by software management systems. Although the availability of clone resources is growing, current collections are either not complete or not fully sequence-verified. We report an automated pipeline, supported by several software applications that enabled the construction of the first comprehensive sequence-verified plasmid clone resource for more than 96% of protein coding sequences of the genome of F. tularensis, a highly virulent human pathogen and the causative agent of tularemia. This clone resource was applied to a HT protein purification pipeline successfully producing recombinant proteins for 72% of the genes. These methods and resources represent significant technological steps towards exploiting the genomic information of F. tularensis in discovery applications

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

It’s not which school but which set you’re in that matters: the influence of ability-grouping practices on student progress in mathematics

The mathematics achievement of a cohort of 955 students in 42 classes in six schools in London was followed over a four-year period, until they took their GCSEs in the summer of 2000. All six schools were regarded by Ofsted as providing a good standard of education, and all were involved in teacher-training partnerships with universities. Matched data on key stage 3 test scores and GCSE grades were available for 709 students, and these data were analysed in terms of the progress from key stage 3 test scores to GCSE grades. Although there were wide differences between schools in terms of overall GCSE grades, the average progress made by students was similar in all six schools. However, within each school, the progress made during key stage 4 varied greatly from set to set. Comparing students with the same key stage 3 scores, students placed in top sets averaged nearly half a GCSE grade higher than those in the other upper sets, who in turn averaged a third of a grade higher than those in lower sets, who in turn averaged around a third of a grade higher than those students placed in bottom sets. In the four schools that used formal whole-class teaching, the difference in GCSE grades between top and bottom sets, taking key stage 3 scores into account, ranged from just over 1 grade at GCSE to nearly 3 grades. At the schools using small-group and individualised teaching, the differences in value-added between sets were not significant. In two of the schools, a significant proportion of working class students were placed into lower sets than would be indicated by their key stage 3 test scores

Taking the Initiative? TLRP and Educational Research

Evaluating the effects of known subject traits on pediatric GI community structure and function. PCoA of the GI microbial communities of healthy children as a function of Bray-Curtis dissimilarities and 16S-based OTUs (A–D), WGS-based species (E–H), KO groups (I–L), and KEGG pathway profiles (M–P). Variation among profiles was evaluated with respect to known traits, and the percent variation captured by each axis is indicated in parenthesis. Adonis analysis results describe the significance of each trait to overall community variation. (TIF 1.58 kb

Alterations of the Gut Microbial Community Structure and Function With Aging in the Spontaneously Hypertensive Stroke Prone Rat

Gut dysbiosis, a pathological imbalance of bacteria, has been shown to contribute to the development of hypertension (HT), systemic- and neuro-inflammation, and blood-brain barrier (BBB) disruption in spontaneously hypertensive stroke prone rats (SHRSP). However, to date individual species that contribute to HT in the SHRSP model have not been identified. One potential reason, is that nearly all studies of the SHRSP gut microbiota have analyzed samples from rats with established HT. The goal of this study was to examine the SHRSP gut microbiota before, during, and after the onset of hypertension, and in normotensive WKY control rats over the same age range. We hypothesized that we could identify key microbes involved in the development of HT by comparing WKY and SHRSP microbiota during the pre-hypertensive state and longitudinally. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and fecal microbiota analyzed by16S rRNA gene sequencing. SHRSP showed significant elevations in SBP, as compared to WKY, beginning at 8 weeks of age (p \u3c 0.05 at each time point). Bacterial community structure was significantly different between WKY and SHRSP as early as 4 weeks of age, and remained different throughout the study (p = 0.001-0.01). At the phylum level we observed significantly reduced Firmicutes and Deferribacterota, and elevated Bacteroidota, Verrucomicrobiota, and Proteobacteria, in pre-hypertensive SHRSP, as compared to WKY. At the genus level we identified 18 bacteria whose relative abundance was significantly different in SHRSP versus WKY at the pre-hypertensive ages of 4 or 6 weeks. In an attempt to further refine bacterial candidates that might contribute to the SHRSP phenotype, we compared the functional capacity of WKY versus SHRSP microbial communities. We identified significant differences in amino acid metabolism. Using untargeted metabolomics we found significant reductions in metabolites of the tryptophan-kynurenine pathway and increased indole metabolites in SHRSP versus WKY plasma. Overall, we provide further evidence that gut dysbiosis contributes to hypertension in the SHRSP model, and suggest for the first time the potential involvement of tryptophan metabolizing microbes

Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene

Middle ear microbial profiles of indigenous Filipinos with chronic otitis media. All panels compare carriers with non-carriers of the A2ML1 duplication variant. Panel description: (A) ι-diversity by observed OTUs; (B) ι-diversity by the Shannon diversity index; (C) β-diversity from unweighted UniFrac principal coordinate analysis; (D) β-diversity from weighted UniFrac principal coordinate analysis. (PDF 1019 kb