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Search Results: 1 - 10 of 96823 matches for " Jeffrey I. Gordon "
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Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host
Justin L. Sonnenburg,Christina T. L. Chen,Jeffrey I. Gordon
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0040413
Abstract: Probiotics are deliberately ingested preparations of live bacterial species that confer health benefits on the host. Many of these species are associated with the fermentation of dairy products. Despite their increasing use, the molecular details of the impact of various probiotic preparations on resident members of the gut microbiota and the host are generally lacking. To address this issue, we colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the adult human gut microbiota, and Bifidobacterium longum, a minor member but a commonly used probiotic. Simultaneous whole genome transcriptional profiling of both bacterial species in their gut habitat and of the intestinal epithelium, combined with mass-spectrometric analysis of habitat-associated carbohydrates, revealed that the presence of B. longum elicits an expansion in the diversity of polysaccharides targeted for degradation by B. thetaiotaomicron (e.g., mannose- and xylose-containing glycans), and induces host genes involved in innate immunity. Although the overall transcriptome expressed by B. thetaiotaomicron when it encounters B. longum in the cecum is dependent upon the genetic background of the mouse (as assessed by a mixed analysis of variance [ANOVA] model of co-colonization experiments performed in NMRI and C57BL/6J animals), B. thetaiotaomicron's expanded capacity to utilize polysaccharides occurs independently of host genotype, and is also observed with a fermented dairy product-associated strain, Lactobacillus casei. This gnotobiotic mouse model provides a controlled case study of how a resident symbiont and a probiotic species adapt their substrate utilization in response to one another, and illustrates both the generality and specificity of the relationship between a host, a component of its microbiota, and intentionally consumed microbial species.
Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host
Justin L Sonnenburg,Christina T. L Chen,Jeffrey I Gordon
PLOS Biology , 2006, DOI: 10.1371/journal.pbio.0040413
Abstract: Probiotics are deliberately ingested preparations of live bacterial species that confer health benefits on the host. Many of these species are associated with the fermentation of dairy products. Despite their increasing use, the molecular details of the impact of various probiotic preparations on resident members of the gut microbiota and the host are generally lacking. To address this issue, we colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the adult human gut microbiota, and Bifidobacterium longum, a minor member but a commonly used probiotic. Simultaneous whole genome transcriptional profiling of both bacterial species in their gut habitat and of the intestinal epithelium, combined with mass-spectrometric analysis of habitat-associated carbohydrates, revealed that the presence of B. longum elicits an expansion in the diversity of polysaccharides targeted for degradation by B. thetaiotaomicron (e.g., mannose- and xylose-containing glycans), and induces host genes involved in innate immunity. Although the overall transcriptome expressed by B. thetaiotaomicron when it encounters B. longum in the cecum is dependent upon the genetic background of the mouse (as assessed by a mixed analysis of variance [ANOVA] model of co-colonization experiments performed in NMRI and C57BL/6J animals), B. thetaiotaomicron's expanded capacity to utilize polysaccharides occurs independently of host genotype, and is also observed with a fermented dairy product-associated strain, Lactobacillus casei. This gnotobiotic mouse model provides a controlled case study of how a resident symbiont and a probiotic species adapt their substrate utilization in response to one another, and illustrates both the generality and specificity of the relationship between a host, a component of its microbiota, and intentionally consumed microbial species.
Simultaneous Amplicon Sequencing to Explore Co-Occurrence Patterns of Bacterial, Archaeal and Eukaryotic Microorganisms in Rumen Microbial Communities
Sandra Kittelmann, Henning Seedorf, William A. Walters, Jose C. Clemente, Rob Knight, Jeffrey I. Gordon, Peter H. Janssen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0047879
Abstract: Ruminants rely on a complex rumen microbial community to convert dietary plant material to energy-yielding products. Here we developed a method to simultaneously analyze the community's bacterial and archaeal 16S rRNA genes, ciliate 18S rRNA genes and anaerobic fungal internal transcribed spacer 1 genes using 12 DNA samples derived from 11 different rumen samples from three host species (Ovis aries, Bos taurus, Cervus elephas) and multiplex 454 Titanium pyrosequencing. We show that the mixing ratio of the group-specific DNA templates before emulsion PCR is crucial to compensate for differences in amplicon length. This method, in contrast to using a non-specific universal primer pair, avoids sequencing non-targeted DNA, such as plant- or endophyte-derived rRNA genes, and allows increased or decreased levels of community structure resolution for each microbial group as needed. Communities analyzed with different primers always grouped by sample origin rather than by the primers used. However, primer choice had a greater impact on apparent archaeal community structure than on bacterial community structure, and biases for certain methanogen groups were detected. Co-occurrence analysis of microbial taxa from all three domains of life suggested strong within- and between-domain correlations between different groups of microorganisms within the rumen. The approach used to simultaneously characterize bacterial, archaeal and eukaryotic components of a microbiota should be applicable to other communities occupying diverse habitats.
In vitro evaluation of the potential role of sulfite radical in morphine-associated histamine release
Gordon Emma M,Myers Carolyn,Blumer Jeffrey
BMC Pharmacology , 2004, DOI: 10.1186/1471-2210-4-21
Abstract: Background Intravenous morphine use is associated with elevated histamine release leading to bronchoconstriction, edema and hemodynamic instability in some patients. This study evaluated the possibility that sulfite, which is present as a preservative in many morphine preparations, might contribute to histamine release in vitro. Results The human mast cell line, HMC-1, was exposed to various morphine concentrations, in the absence of sulfite, under cell culture conditions. Clinically attained concentrations of morphine (0.018μg/ml and 0.45μg/ml) did not cause increased histamine release from mast cells. There was a significant increase in histamine release when the morphine concentration was increased by 1184-fold (668μg/ml morphine). Histamine release from mast cells exposed to morphine and/or sulfite required the presence of prostaglandin H synthetase. Histamine release in experiments using sulfite-containing morphine solutions was not statistically different from that observed in morphine-only solutions. Conclusion Sulfite in sulfite-containing morphine solutions, at concentrations seen clinically, is not responsible for histamine release in in vitro experiments of the human mast cell line, HMC-1. This does not preclude the fact that sulfite may lead to elevation of histamine levels in vivo.
Abrupt Longitudinal Magnetic Field Changes and Ultraviolet Emissions Accompanying Solar Flares
Brittany Johnstone,Gordon Petrie,Jeffrey Sudol
Physics , 2012, DOI: 10.1088/0004-637X/760/1/29
Abstract: We have used Transition Region and Coronal Explorer (TRACE) 1600 \AA images and Global Oscillation Network Group (GONG) magnetograms to compare ultraviolet (UV) emissions from the chromosphere to longitudinal magnetic field changes in the photosphere during four X-class solar flares. An abrupt, significant, and persistent change in the magnetic field occurred across more than ten pixels in the GONG magnetograms for each flare. These magnetic changes lagged the GOES flare start times in all cases, showing that they were consequences and not causes of the flares. Ultraviolet emissions were spatially coincident with the field changes. The UV emissions tended to lag the GOES start times for the flares, and led the changes in the magnetic field in all pixels except one. The UV emissions led the photospheric field changes by 4 minutes on average with the longest lead being 9 minutes, however, the UV emissions continued for tens of minutes, and more than an hour in some cases, after the field changes were complete. The observations are consistent with the picture in which an Alfv\'{e}n wave from the field reconnection site in the corona propagates field changes outward in all directions near the onset of the impulsive phase, including downwards through the chromosphere and into the photosphere, causing the photospheric field changes, whereas the chromosphere emits in the UV in the form of flare kernels, ribbons and sequential chromospheric brightenings during all phases of the flare.
Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts
Eric C. Martens,Elisabeth C. Lowe,Herbert Chiang,Nicholas A. Pudlo,Meng Wu,Nathan P. McNulty,D. Wade Abbott,Bernard Henrissat,Harry J. Gilbert,David N. Bolam,Jeffrey I. Gordon
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001221
Abstract: Symbiotic bacteria inhabiting the human gut have evolved under intense pressure to utilize complex carbohydrates, primarily plant cell wall glycans in our diets. These polysaccharides are not digested by human enzymes, but are processed to absorbable short chain fatty acids by gut bacteria. The Bacteroidetes, one of two dominant bacterial phyla in the adult gut, possess broad glycan-degrading abilities. These species use a series of membrane protein complexes, termed Sus-like systems, for catabolism of many complex carbohydrates. However, the role of these systems in degrading the chemically diverse repertoire of plant cell wall glycans remains unknown. Here we show that two closely related human gut Bacteroides, B. thetaiotaomicron and B. ovatus, are capable of utilizing nearly all of the major plant and host glycans, including rhamnogalacturonan II, a highly complex polymer thought to be recalcitrant to microbial degradation. Transcriptional profiling and gene inactivation experiments revealed the identity and specificity of the polysaccharide utilization loci (PULs) that encode individual Sus-like systems that target various plant polysaccharides. Comparative genomic analysis indicated that B. ovatus possesses several unique PULs that enable degradation of hemicellulosic polysaccharides, a phenotype absent from B. thetaiotaomicron. In contrast, the B. thetaiotaomicron genome has been shaped by increased numbers of PULs involved in metabolism of host mucin O-glycans, a phenotype that is undetectable in B. ovatus. Binding studies of the purified sensor domains of PUL-associated hybrid two-component systems in conjunction with transcriptional analyses demonstrate that complex oligosaccharides provide the regulatory cues that induce PUL activation and that each PUL is highly specific for a defined cell wall polymer. These results provide a view of how these species have diverged into different carbohydrate niches by evolving genes that target unique suites of available polysaccharides, a theme that likely applies to disparate bacteria from the gut and other habitats.
Direct sequencing of the human microbiome readily reveals community differences
Justin Kuczynski, Elizabeth K Costello, Diana R Nemergut, Jesse Zaneveld, Christian L Lauber, Dan Knights, Omry Koren, Noah Fierer, Scott T Kelley, Ruth E Ley, Jeffrey I Gordon, Rob Knight
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-5-210
Abstract: In the past few years, the availability of improved sequencing methods, including pyrosequencing [1], has revolutionized what we know about the microbes that inhabit our bodies. Although it has been known for decades that our microbial symbionts outnumber our own cellsby about a factor of 10 [2], the differences in the repertoires ofsymbiontsharbored by different healthy individuals, different siteswithin the individual, and by individuals over time are only now coming to light. Initially, it was assumed that a 'core microbiome' existed; that is, that a substantial number of microbial species was shared in each body habitat in all or most humans, and that the genomes of these core species could be used as scaffolds to assemble fragmentary data from short-read shotgun sequencing of microbial community DNA [3].The first three individuals whose gut microbiomes were surveyed using substantial numbers of 16S rRNA genesequences shared few of their species, however [4]. Similarly, observations that a person's left and right hands have only 17% of bacterial species in common, and that two different people's hands share only 13% [5], cast doubt on the concept of a substantial core set of microbial species shared by all or most people. This doubt has been reinforced by recent work that redefines core lineages or genes as 'core' even if shared by relatively few people [6,7]. In fact, on the basis of 16S rRNA geneanalyses we can rule out the possibility that, even within relatively homogeneous small populations of fewer than 100 individuals, everyone's skin-surface communities or gut communities share more than a tiny fraction of species [6-8]. This unanticipated variability in shared community membership, and also in other important aspects of the human microbiome, poses substantial conceptual and computational challenges.Of particular importance for microbiome studies is the following question: what is the effect size? That is, using standard terminology from statistics, how
Moving pictures of the human microbiome
J Gregory Caporaso, Christian L Lauber, Elizabeth K Costello, Donna Berg-Lyons, Antonio Gonzalez, Jesse Stombaugh, Dan Knights, Pawel Gajer, Jacques Ravel, Noah Fierer, Jeffrey I Gordon, Rob Knight
Genome Biology , 2011, DOI: 10.1186/gb-2011-12-5-r50
Abstract: We find that despite stable differences between body sites and individuals, there is pronounced variability in an individual's microbiota across months, weeks and even days. Additionally, only a small fraction of the total taxa found within a single body site appear to be present across all time points, suggesting that no core temporal microbiome exists at high abundance (although some microbes may be present but drop below the detection threshold). Many more taxa appear to be persistent but non-permanent community members.DNA sequencing and computational advances described here provide the ability to go beyond infrequent snapshots of our human-associated microbial ecology to high-resolution assessments of temporal variations over protracted periods, within and between body habitats and individuals. This capacity will allow us to define normal variation and pathologic states, and assess responses to therapeutic interventions.As more attention is paid to viewing ourselves as a supraorganism, comprising interacting microbial and human cellular and genetic components, it is apparent that much more precise understanding is needed of what constitutes normal temporal variations in our microbial community structures and functions. Variation in the human microbiome within and between our various body habitats, lifecycle stages, and cultural settings is largely unexplored. High-resolution time series studies provide a foundation for discriminating between 'normal' perturbations and pathologic states, and between organisms that are simply passing through a body habitat or are entrenched residents of an ecosystem. Similarly, these types of studies are needed to understand the immigration and emigration patterns of microbes between our body sites, between cohabitating individuals, and between ourselves and the myriad of environments we contact on a daily basis [1-3].The densest human microbiome time series reported to date studied the response of distal gut microbial communitie
Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome
Nathan P. McNulty,Meng Wu,Alison R. Erickson,Chongle Pan,Brian K. Erickson,Eric C. Martens,Nicholas A. Pudlo,Brian D. Muegge,Bernard Henrissat,Robert L. Hettich,Jeffrey I. Gordon
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001637
Abstract: The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising >90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism's 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight into how gut microbes adapt to dietary perturbations at both a community level and from the perspective of a well-adapted symbiont with exceptional saccharolytic capabilities, and illustrate the value of artificial communities.
Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts
Eric C. Martens equal contributor ,Elisabeth C. Lowe equal contributor,Herbert Chiang,Nicholas A. Pudlo,Meng Wu,Nathan P. McNulty,D. Wade Abbott,Bernard Henrissat,Harry J. Gilbert,David N. Bolam ,Jeffrey I. Gordon
PLOS Biology , 2011, DOI: 10.1371/journal.pbio.1001221
Abstract: Symbiotic bacteria inhabiting the human gut have evolved under intense pressure to utilize complex carbohydrates, primarily plant cell wall glycans in our diets. These polysaccharides are not digested by human enzymes, but are processed to absorbable short chain fatty acids by gut bacteria. The Bacteroidetes, one of two dominant bacterial phyla in the adult gut, possess broad glycan-degrading abilities. These species use a series of membrane protein complexes, termed Sus-like systems, for catabolism of many complex carbohydrates. However, the role of these systems in degrading the chemically diverse repertoire of plant cell wall glycans remains unknown. Here we show that two closely related human gut Bacteroides, B. thetaiotaomicron and B. ovatus, are capable of utilizing nearly all of the major plant and host glycans, including rhamnogalacturonan II, a highly complex polymer thought to be recalcitrant to microbial degradation. Transcriptional profiling and gene inactivation experiments revealed the identity and specificity of the polysaccharide utilization loci (PULs) that encode individual Sus-like systems that target various plant polysaccharides. Comparative genomic analysis indicated that B. ovatus possesses several unique PULs that enable degradation of hemicellulosic polysaccharides, a phenotype absent from B. thetaiotaomicron. In contrast, the B. thetaiotaomicron genome has been shaped by increased numbers of PULs involved in metabolism of host mucin O-glycans, a phenotype that is undetectable in B. ovatus. Binding studies of the purified sensor domains of PUL-associated hybrid two-component systems in conjunction with transcriptional analyses demonstrate that complex oligosaccharides provide the regulatory cues that induce PUL activation and that each PUL is highly specific for a defined cell wall polymer. These results provide a view of how these species have diverged into different carbohydrate niches by evolving genes that target unique suites of available polysaccharides, a theme that likely applies to disparate bacteria from the gut and other habitats.
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