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

Randomized Trial of Pacemaker and Lead System for Safe Scanning at 1.5 Tesla

BackgroundMagnetic resonance imaging (MRI) of pacemakers is a relative contraindication because of the risks to the patient from potentially hazardous interactions between the MRI and the pacemaker system. Chest scans (ie, cardiac magnetic resonance scans) are of particular importance and higher risk. The previously Food and Drug Administration-approved magnetic resonance conditional system includes positioning restrictions, limiting the powerful utility of MRI.ObjectiveTo confirm the safety and effectiveness of a pacemaker system designed for safe whole body MRI without MRI scan positioning restrictions.MethodsPrimary eligibility criteria included standard dual-chamber pacing indications. Patients (n = 263) were randomized in a 2:1 ratio to undergo 16 chest and head scans at 1.5 T between 9 and 12 weeks postimplant (n = 177) or to not undergo MRI (n = 86) post-implant. Evaluation of the pacemaker system occurred immediately before, during (monitoring), and after MRI, 1-week post-MRI, and 1-month post-MRI, and similarly for controls. Primary end points measured the MRI-related complication-free rate for safety and compared pacing capture threshold between MRI and control subjects for effectiveness.ResultsThere were no MRI-related complications during or after MRI in subjects undergoing MRI (n = 148). Differences in pacing capture threshold values from pre-MRI to 1-month post-MRI were minimal and similar between the MRI and control groups.ConclusionsThis randomized trial demonstrates that the Advisa MRI pulse generator and CapSureFix MRI 5086MRI lead system is safe and effective in the 1.5 T MRI environment without positioning restrictions for MRI scans or limitations of body parts scanned

Delivering sustained, coordinated and integrated observations of the Southern Ocean for global impact

The Southern Ocean is disproportionately important in its effect on the Earth system, impacting climatic, biogeochemical, and ecological systems, which makes recent observed changes to this system cause for global concern. The enhanced understanding and improvements in predictive skill needed for understanding and projecting future states of the Southern Ocean require sustained observations. Over the last decade, the Southern Ocean Observing System (SOOS) has established networks for enhancing regional coordination and research community groups to advance development of observing system capabilities. These networks support delivery of the SOOS 20-year vision, which is to develop a circumpolar system that ensures time series of key variables, and delivers the greatest impact from data to all key end-users. Although the Southern Ocean remains one of the least-observed ocean regions, enhanced international coordination and advances in autonomous platforms have resulted in progress toward sustained observations of this region. Since 2009, the Southern Ocean community has deployed over 5700 observational platforms south of 40°S. Large-scale, multi-year or sustained, multidisciplinary efforts have been supported and are now delivering observations of essential variables at space and time scales that enable assessment of changes being observed in Southern Ocean systems. The improved observational coverage, however, is predominantly for the open ocean, encompasses the summer, consists of primarily physical oceanographic variables, and covers surface to 2000 m. Significant gaps remain in observations of the ice-impacted ocean, the sea ice, depths >2000 m, the air-ocean-ice interface, biogeochemical and biological variables, and for seasons other than summer. Addressing these data gaps in a sustained way requires parallel advances in coordination networks, cyberinfrastructure and data management tools, observational platform and sensor technology, two-way platform interrogation and data-transmission technologies, modeling frameworks, intercalibration experiments, and development of internationally agreed sampling standards and requirements of key variables. This paper presents a community statement on the major scientific and observational progress of the last decade, and importantly, an assessment of key priorities for the coming decade, toward achieving the SOOS vision and delivering essential data to all end-users.Fil: Newman, Louise. University of Tasmania; AustraliaFil: Heil, Petra. Australian Antarctic Division; Australia. Antarctic Climate And Ecosystems Cooperative Research Centre; AustraliaFil: Trebilco, Rowan. Australian Antarctic Division; Australia. Antarctic Climate And Ecosystems Cooperative Research Centre; AustraliaFil: Katsumata, Katsuro. Japan Agency For Marine earth Science And Technology; JapónFil: Constable, Andrew J.. Antarctic Climate And Ecosystems Cooperative Research Centre; Australia. Australian Antarctic Division; AustraliaFil: Wijk, Esmee van. Commonwealth Scientific And Industrial Research Organization; Australia. Antarctic Climate And Ecosystems Cooperative Research Centre; AustraliaFil: Assmann, Karen. University Goteborg; SueciaFil: Beja, Joana. British Oceanographic Data Centre; AustraliaFil: Bricher, Phillippa. University of Tasmania; AustraliaFil: Coleman, Richard. University of Tasmania; AustraliaFil: Costa, Daniel. University of California; Estados UnidosFil: Diggs, Steve. University of California; Estados UnidosFil: Farneti, Riccardo. The Abdus Salam; Italia. The Abdus Salam. International Centre for Theoretical Physics; ItaliaFil: Fawcett, Sarah. University of Cape Town; SudáfricaFil: Gille, Sarah. University of California; Estados UnidosFil: Hendry, Katharine R.. University of Bristol; Reino UnidoFil: Henley, Sian F.. University of Edinburgh; Reino UnidoFil: Hofmann, Eileen. Old Dominion University; Estados UnidosFil: Maksym, Ted. University of California; Estados UnidosFil: Mazloff, Matthew. University of California; Estados UnidosFil: Meijers, Andrew J.. British Antartic Survey; Reino UnidoFil: Meredith, Michael. British Antartic Survey; Reino UnidoFil: Moreau, Sebastien. Norwegian Polar Institute; NoruegaFil: Ozsoy, Burcu. Istanbul Teknik Üniversitesi; TurquíaFil: Robertson, Robin. Xiamen University; ChinaFil: Schloss, Irene Ruth. Universidad Nacional de Tierra del Fuego; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Schofield, Oscar. State University of New Jersey; Estados UnidosFil: Shi, Jiuxin. Ocean University Of China; ChinaFil: Sikes, Elisabeth L.. State University of New Jersey; Estados UnidosFil: Smith, Inga J.. University of Otago; Nueva Zeland

Novel Bacterial Taxa in the Human Microbiome

The human gut harbors thousands of bacterial taxa. A profusion of metagenomic sequence data has been generated from human stool samples in the last few years, raising the question of whether more taxa remain to be identified. We assessed metagenomic data generated by the Human Microbiome Project Consortium to determine if novel taxa remain to be discovered in stool samples from healthy individuals. To do this, we established a rigorous bioinformatics pipeline that uses sequence data from multiple platforms (Illumina GAIIX and Roche 454 FLX Titanium) and approaches (whole-genome shotgun and 16S rDNA amplicons) to validate novel taxa. We applied this approach to stool samples from 11 healthy subjects collected as part of the Human Microbiome Project. We discovered several low-abundance, novel bacterial taxa, which span three major phyla in the bacterial tree of life. We determined that these taxa are present in a larger set of Human Microbiome Project subjects and are found in two sampling sites (Houston and St. Louis). We show that the number of false-positive novel sequences (primarily chimeric sequences) would have been two orders of magnitude higher than the true number of novel taxa without validation using multiple datasets, highlighting the importance of establishing rigorous standards for the identification of novel taxa in metagenomic data. The majority of novel sequences are related to the recently discovered genus Barnesiella, further encouraging efforts to characterize the members of this genus and to study their roles in the microbial communities of the gut. A better understanding of the effects of less-abundant bacteria is important as we seek to understand the complex gut microbiome in healthy individuals and link changes in the microbiome to disease

Assessment of Microbial Diversity in Biofilms Recovered from Endotracheal Tubes Using Culture Dependent and Independent Approaches

Ventilator-associated pneumonia (VAP) is a common nosocomial infection in mechanically ventilated patients. Biofilm formation is one of the mechanisms through which the endotracheal tube (ET) facilitates bacterial contamination of the lower airways. In the present study, we analyzed the composition of the ET biofilm flora by means of culture dependent and culture independent (16 S rRNA gene clone libraries and pyrosequencing) approaches. Overall, the microbial diversity was high and members of different phylogenetic lineages were detected (Actinobacteria, beta-Proteobacteria, Candida spp., Clostridia, epsilon-Proteobacteria, Firmicutes, Fusobacteria and gamma-Proteobacteria). Culture dependent analysis, based on the use of selective growth media and conventional microbiological tests, resulted in the identification of typical aerobic nosocomial pathogens which are known to play a role in the development of VAP, e.g. Staphylococcus aureus and Pseudomonas aeruginosa. Other opportunistic pathogens were also identified, including Staphylococcus epidermidis and Kocuria varians. In general, there was little correlation between the results obtained by sequencing 16 S rRNA gene clone libraries and by cultivation. Pyrosequencing of PCR amplified 16 S rRNA genes of four selected samples resulted in the identification of a much wider variety of bacteria. The results from the pyrosequencing analysis suggest that these four samples were dominated by members of the normal oral flora such as Prevotella spp., Peptostreptococcus spp. and lactic acid bacteria. A combination of methods is recommended to obtain a complete picture of the microbial diversity of the ET biofilm

Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease

Background: Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders. Methodology/Principal Findings: We applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children’s Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn’s disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity). Conclusions/Significance: Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients.Natural Sciences and Engineering Research Council of Canada (Award NSERC PGS D)National Institutes of Health (U.S.) (1-R21-A1084032-01A1

Loss of Sex and Age Driven Differences in the Gut Microbiome Characterize Arthritis-Susceptible *0401 Mice but Not Arthritis-Resistant *0402 Mice

<div><h3>Background</h3><p>HLA-DRB1*0401 is associated with susceptibility, while HLA-DRB1*0402 is associated with resistance to developing rheumatoid arthritis (RA) and collagen-induced arthritis in humans and transgenic mice respectively. The influence of gut-joint axis has been suggested in RA, though not yet proven.</p> <h3>Methodology/Principal Findings</h3><p>We have used HLA transgenic mice carrying arthritis susceptible and -resistant HLA-DR genes to explore if genetic factors and their interaction with gut flora gut can be used to predict susceptibility to develop arthritis. Pyrosequencing of the 16S rRNA gene from the fecal microbiomes of DRB1*0401 and DRB1*0402 transgenic mice revealed that the guts of *0401 mice is dominated by a Clostridium-like bacterium, whereas the guts of *0402 mice are enriched for members of the <em>Porphyromonadaceae</em> family and <em>Bifidobacteria</em>. DRB1*0402 mice harbor a dynamic sex and age-influenced gut microbiome while DRB1*0401 mice did not show age and sex differences in gut microbiome even though they had altered gut permeability. Cytokine transcripts, measured by rtPCR, in jejuna showed differential TH17 regulatory network gene transcripts in *0401 and *0402 mice.</p> <h3>Conclusions/Significance</h3><p>We have demonstrated for the first time that HLA genes in association with the gut microbiome may determine the immune environment and that the gut microbiome might be a potential biomarker as well as contributor for susceptibility to arthritis. Identification of pathogenic commensal bacteria would provide new understanding of disease pathogenesis, thereby leading to novel approaches for therapy.</p> </div

Identifying Low pH Active and Lactate-Utilizing Taxa within Oral Microbiome Communities from Healthy Children Using Stable Isotope Probing Techniques

<div><h3>Background</h3><p>Many human microbial infectious diseases including dental caries are polymicrobial in nature. How these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral bacteria have been characterized <em>in vitro</em>, their physiology within the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these species remain uncultivated to date with little known besides their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated species will remain enigmatic despite their apparent disease correlation. To start addressing these knowledge gaps, we applied a combination of Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for <em>in vitro</em> temporal monitoring of metabolites and identification of metabolically active and inactive bacterial species.</p> <h3>Methodology/Principal Findings</h3><p>Supragingival plaque samples from caries-free children incubated with ¹³C-substrates under imposed healthy (buffered, pH 7) and diseased states (pH 5.5 and pH 4.5) produced lactate as the dominant organic acid from glucose metabolism. Rapid lactate utilization upon glucose depletion was observed under pH 7 conditions. SIP analyses revealed a number of genera containing cultured and uncultivated taxa with metabolic capabilities at pH 5.5. The diversity of active species decreased significantly at pH 4.5 and was dominated by <em>Lactobacillus</em> and <em>Propionibacterium</em> species, both of which have been previously found within carious lesions from children.</p> <h3>Conclusions/Significance</h3><p>Our approach allowed for identification of species that metabolize carbohydrates under different pH conditions and supports the importance of Lactobacilli and Propionibacterium in the development of childhood caries. Identification of species within healthy subjects that are active at low pH can lead to a better understanding of oral caries onset and generate appropriate targets for preventative measures in the early stages.</p> </div

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies