@article {pmid17943116,
year = {2007},
author = {Turnbaugh, PJ and Ley, RE and Hamady, M and Fraser-Liggett, CM and Knight, R and Gordon, JI},
title = {The human microbiome project.},
journal = {Nature},
volume = {449},
number = {7164},
pages = {804-810},
pmid = {17943116},
issn = {1476-4687},
support = {P30 DK056341/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Biodiversity ; Genome, Bacterial/genetics ; Genomics ; Humans ; Intestines/cytology/immunology/*microbiology ; *Metagenome/genetics/immunology ; Mice ; Sequence Analysis, DNA ; },
abstract = {A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.},
}

Animals
Biodiversity
Genome, Bacterial/genetics
Genomics
Humans
Intestines/cytology/immunology/*microbiology
*Metagenome/genetics/immunology
Mice
Sequence Analysis, DNA

@article {pmid18714051,
year = {2008},
author = {Friedrich, MJ},
title = {Microbiome project seeks to understand human body's microscopic residents.},
journal = {JAMA},
volume = {300},
number = {7},
pages = {777-778},
doi = {10.1001/jama.300.7.777},
pmid = {18714051},
issn = {1538-3598},
mesh = {*Disease Susceptibility ; Homeostasis ; Host-Pathogen Interactions ; Humans ; *Metagenome ; Microbiology ; Symbiosis ; Virulence ; },
}

*Disease Susceptibility
Homeostasis
Host-Pathogen Interactions
Humans
*Metagenome
Microbiology
Symbiosis
Virulence

@article {pmid18794915,
year = {2008},
author = {Ley, RE and Lozupone, CA and Hamady, M and Knight, R and Gordon, JI},
title = {Worlds within worlds: evolution of the vertebrate gut microbiota.},
journal = {Nature reviews. Microbiology},
volume = {6},
number = {10},
pages = {776-788},
pmid = {18794915},
issn = {1740-1534},
support = {T32GM065103/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Bacteria/classification/genetics/isolation & purification ; *Bacterial Physiological Phenomena ; *Biological Evolution ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Metagenome/*genetics ; RNA, Ribosomal, 16S/analysis/genetics ; Vertebrates/*anatomy & histology ; },
abstract = {In this Analysis we use published 16S ribosomal RNA gene sequences to compare the bacterial assemblages that are associated with humans and other mammals, metazoa and free-living microbial communities that span a range of environments. The composition of the vertebrate gut microbiota is influenced by diet, host morphology and phylogeny, and in this respect the human gut bacterial community is typical of an omnivorous primate. However, the vertebrate gut microbiota is different from free-living communities that are not associated with animal body habitats. We propose that the recently initiated international Human Microbiome Project should strive to include a broad representation of humans, as well as other mammalian and environmental samples, as comparative analyses of microbiotas and their microbiomes are a powerful way to explore the evolutionary history of the biosphere.},
}

Animals
Bacteria/classification/genetics/isolation & purification
*Bacterial Physiological Phenomena
*Biological Evolution
Gastrointestinal Tract/metabolism/*microbiology
Humans
Metagenome/*genetics
RNA, Ribosomal, 16S/analysis/genetics
Vertebrates/*anatomy & histology

@article {pmid18806222,
year = {2008},
author = {Lozupone, CA and Hamady, M and Cantarel, BL and Coutinho, PM and Henrissat, B and Gordon, JI and Knight, R},
title = {The convergence of carbohydrate active gene repertoires in human gut microbes.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {105},
number = {39},
pages = {15076-15081},
pmid = {18806222},
issn = {1091-6490},
support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; DK78669/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; },
mesh = {Archaea/classification/*genetics/isolation & purification ; Bacteria/classification/*genetics/isolation & purification ; Carbohydrates/biosynthesis/genetics ; Cluster Analysis ; Gene Transfer, Horizontal ; *Genes, Archaeal ; *Genes, Bacterial ; Genetic Variation ; Glycoside Hydrolases/*genetics ; Glycosyltransferases/*genetics ; Humans ; Intestines/*microbiology ; Multigene Family ; Phylogeny ; },
abstract = {The extreme variation in gene content among phylogenetically related microorganisms suggests that gene acquisition, expansion, and loss are important evolutionary forces for adaptation to new environments. Accordingly, phylogenetically disparate organisms that share a habitat may converge in gene content as they adapt to confront shared challenges. This response should be especially pronounced for functional genes that are important for survival in a particular habitat. We illustrate this principle by showing that the repertoires of two different types of carbohydrate-active enzymes, glycoside hydrolases and glycosyltransferases, have converged in bacteria and archaea that live in the human gut and that this convergence is largely due to horizontal gene transfer rather than gene family expansion. We also identify gut microbes that may have more similar dietary niches in the human gut than would be expected based on phylogeny. The techniques used to obtain these results should be broadly applicable to understanding the functional genes and evolutionary processes important for adaptation in many environments and useful for interpreting the large number of reference microbial genome sequences being generated for the International Human Microbiome Project.},
}

Archaea/classification/*genetics/isolation & purification
Bacteria/classification/*genetics/isolation & purification
Carbohydrates/biosynthesis/genetics
Cluster Analysis
Gene Transfer, Horizontal
*Genes, Archaeal
*Genes, Bacterial
Genetic Variation
Glycoside Hydrolases/*genetics
Glycosyltransferases/*genetics
Humans
Intestines/*microbiology
Multigene Family
Phylogeny

@article {pmid18842991,
year = {2008},
author = {Lampe, JW},
title = {The Human Microbiome Project: getting to the guts of the matter in cancer epidemiology.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {17},
number = {10},
pages = {2523-2524},
doi = {10.1158/1055-9965.EPI-08-0792},
pmid = {18842991},
issn = {1055-9965},
mesh = {Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; *Metagenome ; National Institutes of Health (U.S.) ; Neoplasms/*epidemiology/*microbiology ; United States ; },
}

Disease Susceptibility
Host-Pathogen Interactions
Humans
*Metagenome
National Institutes of Health (U.S.)
Neoplasms/*epidemiology/*microbiology
United States

@article {pmid18971311,
year = {2008},
author = {McGuire, AL and Colgrove, J and Whitney, SN and Diaz, CM and Bustillos, D and Versalovic, J},
title = {Ethical, legal, and social considerations in conducting the Human Microbiome Project.},
journal = {Genome research},
volume = {18},
number = {12},
pages = {1861-1864},
pmid = {18971311},
issn = {1088-9051},
support = {UH2 DK083990/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; },
mesh = {*Bioethics ; Confidentiality ; Human Genome Project/*legislation & jurisprudence ; Humans ; Informed Consent ; Metagenome/*genetics ; Social Change ; United States ; },
}

*Bioethics
Confidentiality
Human Genome Project/*legislation & jurisprudence
Humans
Informed Consent
Metagenome/*genetics
Social Change
United States

@article {pmid19002248,
year = {2008},
author = {Tito, RY and Macmil, S and Wiley, G and Najar, F and Cleeland, L and Qu, C and Wang, P and Romagne, F and Leonard, S and Ruiz, AJ and Reinhard, K and Roe, BA and Lewis, CM},
title = {Phylotyping and functional analysis of two ancient human microbiomes.},
journal = {PloS one},
volume = {3},
number = {11},
pages = {e3703},
pmid = {19002248},
issn = {1932-6203},
mesh = {Bacteria/classification/isolation & purification ; DNA, Bacterial/analysis ; Evolution, Molecular ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Geography ; Humans ; Metagenome/*genetics ; Mexico ; *Phylogeny ; },
abstract = {BACKGROUND: The Human Microbiome Project (HMP) is one of the U.S. National Institutes of Health Roadmap for Medical Research. Primary interests of the HMP include the distinctiveness of different gut microbiomes, the factors influencing microbiome diversity, and the functional redundancies of the members of human microbiotas. In this present work, we contribute to these interests by characterizing two extinct human microbiotas.

We examine two paleofecal samples originating from cave deposits in Durango Mexico and dating to approximately 1300 years ago. Contamination control is a serious issue in ancient DNA research; we use a novel approach to control contamination. After we determined that each sample originated from a different human, we generated 45 thousand shotgun DNA sequencing reads. The phylotyping and functional analysis of these reads reveals a signature consistent with the modern gut ecology. Interestingly, inter-individual variability for phenotypes but not functional pathways was observed. The two ancient samples have more similar functional profiles to each other than to a recently published profile for modern humans. This similarity could not be explained by a chance sampling of the databases.

CONCLUSIONS/SIGNIFICANCE: We conduct a phylotyping and functional analysis of ancient human microbiomes, while providing novel methods to control for DNA contamination and novel hypotheses about past microbiome biogeography. We postulate that natural selection has more of an influence on microbiome functional profiles than it does on the species represented in the microbial ecology. We propose that human microbiomes were more geographically structured during pre-Columbian times than today.},
}

Bacteria/classification/isolation & purification
DNA, Bacterial/analysis
Evolution, Molecular
Gastrointestinal Tract/*microbiology
Genome, Bacterial
Geography
Humans
Metagenome/*genetics
Mexico
*Phylogeny

@article {pmid19004758,
year = {2008},
author = {Fierer, N and Hamady, M and Lauber, CL and Knight, R},
title = {The influence of sex, handedness, and washing on the diversity of hand surface bacteria.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {105},
number = {46},
pages = {17994-17999},
pmid = {19004758},
issn = {1091-6490},
support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; P01DK078669/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; },
mesh = {Bacteria/*genetics ; Functional Laterality/*physiology ; *Genetic Variation ; Hand/*microbiology ; Humans ; *Sex Characteristics ; *Skin Care ; },
abstract = {Bacteria thrive on and within the human body. One of the largest human-associated microbial habitats is the skin surface, which harbors large numbers of bacteria that can have important effects on health. We examined the palmar surfaces of the dominant and nondominant hands of 51 healthy young adult volunteers to characterize bacterial diversity on hands and to assess its variability within and between individuals. We used a novel pyrosequencing-based method that allowed us to survey hand surface bacterial communities at an unprecedented level of detail. The diversity of skin-associated bacterial communities was surprisingly high; a typical hand surface harbored >150 unique species-level bacterial phylotypes, and we identified a total of 4,742 unique phylotypes across all of the hands examined. Although there was a core set of bacterial taxa commonly found on the palm surface, we observed pronounced intra- and interpersonal variation in bacterial community composition: hands from the same individual shared only 17% of their phylotypes, with different individuals sharing only 13%. Women had significantly higher diversity than men, and community composition was significantly affected by handedness, time since last hand washing, and an individual's sex. The variation within and between individuals in microbial ecology illustrated by this study emphasizes the challenges inherent in defining what constitutes a "healthy" bacterial community; addressing these challenges will be critical for the International Human Microbiome Project.},
}

Bacteria/*genetics
Functional Laterality/*physiology
*Genetic Variation
Hand/*microbiology
Humans
*Sex Characteristics
*Skin Care

@article {pmid19023400,
year = {2008},
author = {Huse, SM and Dethlefsen, L and Huber, JA and Mark Welch, D and Relman, DA and Sogin, ML},
title = {Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing.},
journal = {PLoS genetics},
volume = {4},
number = {11},
pages = {e1000255},
pmid = {19023400},
issn = {1553-7404},
support = {DP1 OD000964/OD/NIH HHS/United States ; P50 ES012742/ES/NIEHS NIH HHS/United States ; 1 P50 ES012742-01/ES/NIEHS NIH HHS/United States ; },
mesh = {Bacteria/*classification/genetics ; Biodiversity ; Classification/methods ; Humans ; Metagenome/genetics ; RNA, Ribosomal/*genetics ; Sequence Analysis, DNA ; Sequence Tagged Sites ; },
abstract = {Massively parallel pyrosequencing of hypervariable regions from small subunit ribosomal RNA (SSU rRNA) genes can sample a microbial community two or three orders of magnitude more deeply per dollar and per hour than capillary sequencing of full-length SSU rRNA. As with full-length rRNA surveys, each sequence read is a tag surrogate for a single microbe. However, rather than assigning taxonomy by creating gene trees de novo that include all experimental sequences and certain reference taxa, we compare the hypervariable region tags to an extensive database of rRNA sequences and assign taxonomy based on the best match in a Global Alignment for Sequence Taxonomy (GAST) process. The resulting taxonomic census provides information on both composition and diversity of the microbial community. To determine the effectiveness of using only hypervariable region tags for assessing microbial community membership, we compared the taxonomy assigned to the V3 and V6 hypervariable regions with the taxonomy assigned to full-length SSU rRNA sequences isolated from both the human gut and a deep-sea hydrothermal vent. The hypervariable region tags and full-length rRNA sequences provided equivalent taxonomy and measures of relative abundance of microbial communities, even for tags up to 15% divergent from their nearest reference match. The greater sampling depth per dollar afforded by massively parallel pyrosequencing reveals many more members of the "rare biosphere" than does capillary sequencing of the full-length gene. In addition, tag sequencing eliminates cloning bias and the sequences are short enough to be completely sequenced in a single read, maximizing the number of organisms sampled in a run while minimizing chimera formation. This technique allows the cost-effective exploration of changes in microbial community structure, including the rare biosphere, over space and time and can be applied immediately to initiatives, such as the Human Microbiome Project.},
}

Bacteria/*classification/genetics
Biodiversity
Classification/methods
Humans
Metagenome/genetics
RNA, Ribosomal/*genetics
Sequence Analysis, DNA
Sequence Tagged Sites

@article {pmid19115471,
year = {2009},
author = {Mai, V and Draganov, PV},
title = {Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health.},
journal = {World journal of gastroenterology},
volume = {15},
number = {1},
pages = {81-85},
pmid = {19115471},
issn = {2219-2840},
mesh = {Animals ; Colorectal Neoplasms/etiology/microbiology ; Diabetes Mellitus/etiology/microbiology ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology ; Intestines/*microbiology ; Metagenome/*physiology ; Obesity/microbiology ; Probiotics/therapeutic use ; },
abstract = {The complex gut microbial flora harbored by individuals (microbiota) has long been proposed to contribute to intestinal health as well as disease. Pre- and probiotic products aimed at improving health by modifying microbiota composition have already become widely available and acceptance of these products appears to be on the rise. However, although required for the development of effective microbiota based interventions, our basic understanding of microbiota variation on a population level and its dynamics within individuals is still rudimentary. Powerful new parallel sequence technologies combined with other efficient molecular microbiota analysis methods now allow for comprehensive analysis of microbiota composition in large human populations. Recent findings in the field strongly suggest that microbiota contributes to the development of obesity, atopic diseases, inflammatory bowel diseases and intestinal cancers. Through the ongoing National Institutes of Health Roadmap 'Human Microbiome Project' and similar projects in other parts of the world, a large coordinated effort is currently underway to study how microbiota can impact human health. Translating findings from these studies into effective interventions that can improve health, possibly personalized based on an individuals existing microbiota, will be the task for the next decade(s).},
}

Animals
Colorectal Neoplasms/etiology/microbiology
Diabetes Mellitus/etiology/microbiology
Humans
Inflammatory Bowel Diseases/etiology/microbiology
Intestines/*microbiology
Metagenome/*physiology
Obesity/microbiology
Probiotics/therapeutic use

@article {pmid19147530,
year = {2009},
author = {Hattori, M and Taylor, TD},
title = {The human intestinal microbiome: a new frontier of human biology.},
journal = {DNA research : an international journal for rapid publication of reports on genes and genomes},
volume = {16},
number = {1},
pages = {1-12},
pmid = {19147530},
issn = {1756-1663},
mesh = {Humans ; Inflammatory Bowel Diseases/genetics/microbiology ; Intestinal Mucosa/metabolism/microbiology ; Intestines/*microbiology ; *Metagenome ; Models, Biological ; },
abstract = {To analyze the vast number and variety of microorganisms inhabiting the human intestine, emerging metagenomic technologies are extremely powerful. The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, helping to maintain their homeostasis and can be causative of various diseases, such as inflammatory bowel disease and obesity. A simplified animal model system has provided the mechanistic basis for the molecular interactions that occur at the interface between such microbes and host intestinal epithelia. Through metagenomic analysis, it is now possible to comprehensively explore the genetic nature of the intestinal microbiome, the mutually interacting system comprising the host cells and the residing microbial community. The human microbiome project was recently launched as an international collaborative research effort to further promote this newly developing field and to pave the way to a new frontier of human biology, which will provide new strategies for the maintenance of human health.},
}

Humans
Inflammatory Bowel Diseases/genetics/microbiology
Intestinal Mucosa/metabolism/microbiology
Intestines/*microbiology
*Metagenome
Models, Biological

@article {pmid19264858,
year = {2009},
author = {Petrosino, JF and Highlander, S and Luna, RA and Gibbs, RA and Versalovic, J},
title = {Metagenomic pyrosequencing and microbial identification.},
journal = {Clinical chemistry},
volume = {55},
number = {5},
pages = {856-866},
pmid = {19264858},
issn = {1530-8561},
support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; P30 DK56338/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; R21AT003482/AT/NCCIH NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; },
mesh = {Computational Biology ; DNA, Bacterial/chemistry/genetics ; Genomics/*methods ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/chemistry/genetics ; Sequence Analysis, DNA/*methods ; },
abstract = {BACKGROUND: The Human Microbiome Project has ushered in a new era for human metagenomics and high-throughput next-generation sequencing strategies.

CONTENT: This review describes evolving strategies in metagenomics, with a special emphasis on the core technology of DNA pyrosequencing. The challenges of microbial identification in the context of microbial populations are discussed. The development of next-generation pyrosequencing strategies and the technical hurdles confronting these methodologies are addressed. Bioinformatics-related topics include taxonomic systems, sequence databases, sequence-alignment tools, and classifiers. DNA sequencing based on 16S rRNA genes or entire genomes is summarized with respect to potential pyrosequencing applications.

SUMMARY: Both the approach of 16S rDNA amplicon sequencing and the whole-genome sequencing approach may be useful for human metagenomics, and numerous bioinformatics tools are being deployed to tackle such vast amounts of microbiological sequence diversity. Metagenomics, or genetic studies of microbial communities, may ultimately contribute to a more comprehensive understanding of human health, disease susceptibilities, and the pathophysiology of infectious and immune-mediated diseases.},
}

Computational Biology
DNA, Bacterial/chemistry/genetics
Genomics/*methods
Humans
*Metagenome
RNA, Ribosomal, 16S/chemistry/genetics
Sequence Analysis, DNA/*methods

@article {pmid19340927,
year = {2009},
author = {Hsiao, WW and Fraser-Liggett, CM},
title = {Human Microbiome Project--paving the way to a better understanding of ourselves and our microbes.},
journal = {Drug discovery today},
volume = {14},
number = {7-8},
pages = {331-333},
doi = {10.1016/j.drudis.2009.03.001},
pmid = {19340927},
issn = {1878-5832},
mesh = {*Disease Susceptibility ; Genome, Bacterial ; Host-Pathogen Interactions ; Humans ; *Metagenome ; Symbiosis ; Virulence ; },
}

*Disease Susceptibility
Genome, Bacterial
Host-Pathogen Interactions
Humans
*Metagenome
Symbiosis
Virulence

@article {pmid19393196,
year = {2009},
author = {Proal, AD and Albert, PJ and Marshall, T},
title = {Autoimmune disease in the era of the metagenome.},
journal = {Autoimmunity reviews},
volume = {8},
number = {8},
pages = {677-681},
doi = {10.1016/j.autrev.2009.02.016},
pmid = {19393196},
issn = {1873-0183},
mesh = {Alkanesulfonic Acids/metabolism ; Autoantibodies/immunology ; Autoimmune Diseases/genetics/metabolism/*microbiology ; Bacteria/genetics/*metabolism ; DNA, Bacterial/metabolism ; *Genomics ; Humans ; Immunity, Innate ; Metabolome/*genetics ; *Metabolomics ; Metagenome/*genetics ; },
abstract = {Studies of autoimmune disease have focused on the characteristics of the identifiable antibodies. But as our knowledge of the genes associated with the disease states expands, we understand that humans must be viewed as superorganisms in which a plethora of bacterial genomes - a metagenome - work in tandem with our own. The NIH has estimated that 90% of the cells in Homo sapiens are microbial and not human in origin. Some of these microbes create metabolites that interfere with the expression of genes associated with autoimmune disease. Thus, we must re-examine how human gene transcription is affected by the plethora of microbial metabolites. We can no longer assume that antibodies generated in autoimmune disease are created solely as autoantibodies to human DNA. Evidence is now emerging that the human microbiota accumulates during a lifetime, and a variety of persistence mechanisms are coming to light. In one model, obstruction of VDR nuclear-receptor-transcription prevents the innate immune system from making key antimicrobials, allowing the microbes to persist. Genes from these microbes must necessarily impact disease progression. Recent efforts to decrease this VDR-perverting microbiota in patients with autoimmune disease have resulted in reversal of autoimmune processes. As the NIH Human Microbiome Project continues to better characterize the human metagenome, new insights into autoimmune pathogenesis are beginning to emerge.},
}

Alkanesulfonic Acids/metabolism
Autoantibodies/immunology
Autoimmune Diseases/genetics/metabolism/*microbiology
Bacteria/genetics/*metabolism
DNA, Bacterial/metabolism
*Genomics
Humans
Immunity, Innate
Metabolome/*genetics
*Metabolomics
Metagenome/*genetics

@article {pmid19491241,
year = {2009},
author = {Turnbaugh, PJ and Gordon, JI},
title = {The core gut microbiome, energy balance and obesity.},
journal = {The Journal of physiology},
volume = {587},
number = {Pt 17},
pages = {4153-4158},
pmid = {19491241},
issn = {1469-7793},
support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; UL1 RR024992/RR/NCRR NIH HHS/United States ; DK078669/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; },
mesh = {Animals ; *Energy Metabolism ; Humans ; Intestines/*microbiology/*physiopathology ; Metagenome/*physiology ; *Models, Biological ; Obesity/*microbiology/pathology/*physiopathology ; },
abstract = {Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.},
}

Animals
*Energy Metabolism
Humans
Intestines/*microbiology/*physiopathology
Metagenome/*physiology
*Models, Biological
Obesity/*microbiology/pathology/*physiopathology

@article {pmid19507517,
year = {2009},
author = {Hattori, M},
title = {[Disease and metagenomics of intestinal microbiomes].},
journal = {Nihon rinsho. Japanese journal of clinical medicine},
volume = {67},
number = {6},
pages = {1214-1218},
pmid = {19507517},
issn = {0047-1852},
mesh = {Animals ; Bacteria/*genetics ; Disease/etiology ; Humans ; Intestines/*microbiology ; },
abstract = {The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, leading to maintain their homeostasis, and can be causative of various diseases such as inflammatory bowel disease and obesity. A culture-independent approach 'metagenomics' now makes it possible to comprehensively explore the genetic nature of intestinal microbiome (collective genomes of microbes), providing the mechanistic basis for the functional roles of intestinal microbiome. The International Human Microbiome Project was recently launched to further promote this newly developing field, which will provide new strategies for the maintenance of human health.},
}

Animals
Bacteria/*genetics
Disease/etiology
Humans
Intestines/*microbiology

@article {pmid19815760,
year = {2009},
author = {Chain, PS and Grafham, DV and Fulton, RS and Fitzgerald, MG and Hostetler, J and Muzny, D and Ali, J and Birren, B and Bruce, DC and Buhay, C and Cole, JR and Ding, Y and Dugan, S and Field, D and Garrity, GM and Gibbs, R and Graves, T and Han, CS and Harrison, SH and Highlander, S and Hugenholtz, P and Khouri, HM and Kodira, CD and Kolker, E and Kyrpides, NC and Lang, D and Lapidus, A and Malfatti, SA and Markowitz, V and Metha, T and Nelson, KE and Parkhill, J and Pitluck, S and Qin, X and Read, TD and Schmutz, J and Sozhamannan, S and Sterk, P and Strausberg, RL and Sutton, G and Thomson, NR and Tiedje, JM and Weinstock, G and Wollam, A and , and Detter, JC},
title = {Genomics. Genome project standards in a new era of sequencing.},
journal = {Science (New York, N.Y.)},
volume = {326},
number = {5950},
pages = {236-237},
pmid = {19815760},
issn = {1095-9203},
support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; },
mesh = {Computational Biology ; Databases, Nucleic Acid/*standards ; *Genome ; Genomics/*standards ; Sequence Analysis, DNA/*standards ; },
abstract = {More detailed sequence standards that keep up with revolutionary sequencing technologies will aid the research community in evaluating data.},
}

Computational Biology
Databases, Nucleic Acid/*standards
*Genome
Genomics/*standards
Sequence Analysis, DNA/*standards

@article {pmid19819907,
year = {2009},
author = {, and Peterson, J and Garges, S and Giovanni, M and McInnes, P and Wang, L and Schloss, JA and Bonazzi, V and McEwen, JE and Wetterstrand, KA and Deal, C and Baker, CC and Di Francesco, V and Howcroft, TK and Karp, RW and Lunsford, RD and Wellington, CR and Belachew, T and Wright, M and Giblin, C and David, H and Mills, M and Salomon, R and Mullins, C and Akolkar, B and Begg, L and Davis, C and Grandison, L and Humble, M and Khalsa, J and Little, AR and Peavy, H and Pontzer, C and Portnoy, M and Sayre, MH and Starke-Reed, P and Zakhari, S and Read, J and Watson, B and Guyer, M},
title = {The NIH Human Microbiome Project.},
journal = {Genome research},
volume = {19},
number = {12},
pages = {2317-2323},
pmid = {19819907},
issn = {1549-5469},
mesh = {*Bacteria/classification/genetics/isolation & purification ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*genetics ; Mouth/*microbiology ; National Health Programs ; *National Institutes of Health (U.S.) ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/*microbiology ; United States ; Vagina/*microbiology ; },
abstract = {The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.},
}

*Bacteria/classification/genetics/isolation & purification
Female
Gastrointestinal Tract/*microbiology
Humans
Metagenome/*genetics
Mouth/*microbiology
National Health Programs
*National Institutes of Health (U.S.)
RNA, Ribosomal, 16S/genetics
Sequence Analysis, DNA
Skin/*microbiology
United States
Vagina/*microbiology

@article {pmid19968883,
year = {2009},
author = {Aziz, RK},
title = {A hundred-year-old insight into the gut microbiome!.},
journal = {Gut pathogens},
volume = {1},
number = {1},
pages = {21},
pmid = {19968883},
issn = {1757-4749},
abstract = {As the National Institutes of Health-funded Human Microbiome Project enters its second phase, and as a major part of this project focuses on the human gut microbiome and its effects on human health, it might help us to travel a century back in time and examine how microbiologists dealt with microbiome-related challenges similar to those of the 21st century using the tools of their time. An article by Arthur I. Kendall, published in The Journal of Biological Chemistry in November 1909 (Some observations on the study of the intestinal bacteria J Biol Chem 1909, 6:499-507), offers a visionary insight into many of today's hot research questions.},
}

@article {pmid20337064,
year = {2010},
author = {Xue, J and Xiao, LY and Zhou, XD},
title = {[The latest progress in studies of human oral microbiome].},
journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology},
volume = {28},
number = {1},
pages = {5-8},
pmid = {20337064},
issn = {1000-1182},
mesh = {Humans ; *Metagenome ; *Microbiota ; Mouth/*microbiology ; },
abstract = {With the successful implementation of Human Genome Project, more and more scientists started to pay attention on the second genome of human body: Microbiome. This paper will briefly introduce the latest developments of the Human Microbiome Project, the human oral microbiome research, and new technologies of microbial gene research.},
}

Humans
*Metagenome
*Microbiota
Mouth/*microbiology

@article {pmid20418441,
year = {2010},
author = {Pei, AY and Oberdorf, WE and Nossa, CW and Agarwal, A and Chokshi, P and Gerz, EA and Jin, Z and Lee, P and Yang, L and Poles, M and Brown, SM and Sotero, S and Desantis, T and Brodie, E and Nelson, K and Pei, Z},
title = {Diversity of 16S rRNA genes within individual prokaryotic genomes.},
journal = {Applied and environmental microbiology},
volume = {76},
number = {12},
pages = {3886-3897},
pmid = {20418441},
issn = {1098-5336},
support = {R01 AI063477/AI/NIAID NIH HHS/United States ; UH2 CA140233/CA/NCI NIH HHS/United States ; R01AI063477/AI/NIAID NIH HHS/United States ; UH2CA140233/CA/NCI NIH HHS/United States ; },
mesh = {Genes, rRNA/*genetics ; *Genome, Archaeal ; *Genome, Bacterial ; *Polymorphism, Genetic ; RNA, Ribosomal, 16S/*genetics ; },
abstract = {Analysis of intragenomic variation of 16S rRNA genes is a unique approach to examining the concept of ribosomal constraints on rRNA genes; the degree of variation is an important parameter to consider for estimation of the diversity of a complex microbiome in the recently initiated Human Microbiome Project (http://nihroadmap.nih.gov/hmp). The current GenBank database has a collection of 883 prokaryotic genomes representing 568 unique species, of which 425 species contained 2 to 15 copies of 16S rRNA genes per genome (2.22 +/- 0.81). Sequence diversity among the 16S rRNA genes in a genome was found in 235 species (from 0.06% to 20.38%; 0.55% +/- 1.46%). Compared with the 16S rRNA-based threshold for operational definition of species (1 to 1.3% diversity), the diversity was borderline (between 1% and 1.3%) in 10 species and >1.3% in 14 species. The diversified 16S rRNA genes in Haloarcula marismortui (diversity, 5.63%) and Thermoanaerobacter tengcongensis (6.70%) were highly conserved at the 2 degrees structure level, while the diversified gene in B. afzelii (20.38%) appears to be a pseudogene. The diversified genes in the remaining 21 species were also conserved, except for a truncated 16S rRNA gene in "Candidatus Protochlamydia amoebophila." Thus, this survey of intragenomic diversity of 16S rRNA genes provides strong evidence supporting the theory of ribosomal constraint. Taxonomic classification using the 16S rRNA-based operational threshold could misclassify a number of species into more than one species, leading to an overestimation of the diversity of a complex microbiome. This phenomenon is especially seen in 7 bacterial species associated with the human microbiome or diseases.},
}

Genes, rRNA/*genetics
*Genome, Archaeal
*Genome, Bacterial
*Polymorphism, Genetic
RNA, Ribosomal, 16S/*genetics

@article {pmid20471127,
year = {2010},
author = {Candela, M and Maccaferri, S and Turroni, S and Carnevali, P and Brigidi, P},
title = {Functional intestinal microbiome, new frontiers in prebiotic design.},
journal = {International journal of food microbiology},
volume = {140},
number = {2-3},
pages = {93-101},
doi = {10.1016/j.ijfoodmicro.2010.04.017},
pmid = {20471127},
issn = {1879-3460},
mesh = {Animals ; Bacteria/genetics/*metabolism ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; *Metagenome ; Prebiotics/*analysis ; },
abstract = {In this review we focus on the revision of the prebiotic concept in the context of the new metagenomic era. Functional metagenomic data provided by the Human Microbiome Project are revolutionizing the view of the symbiotic relationship between the intestinal microbiota and the human host. A deeper knowledge of the mechanisms that govern the dynamic interplay between diet, intestinal microbiota and host nutrition opens the way to better information on the prebiotic structure-function relationships, tailoring prebiotic formula into specific health attributes. On the other hand, functional genomic studies of the sourdough microbial communities allow to scan the environmental variability to identify novel metabolic traits for the biosynthesis of new potential prebiotic molecules. The integration of the functional analyses provided by the massive sequencing of bacterial genomes and metagenomes will allow the rational production of a desired prebiotic molecule with specific functional properties.},
}

Animals
Bacteria/genetics/*metabolism
Humans
Intestinal Mucosa/metabolism
Intestines/*microbiology
*Metagenome
Prebiotics/*analysis

@article {pmid20624719,
year = {2010},
author = {Chen, T and Yu, WH and Izard, J and Baranova, OV and Lakshmanan, A and Dewhirst, FE},
title = {The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information.},
journal = {Database : the journal of biological databases and curation},
volume = {2010},
number = {},
pages = {baq013},
pmid = {20624719},
issn = {1758-0463},
support = {R21 DE017106/DE/NIDCR NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; DE016937/DE/NIDCR NIH HHS/United States ; DE017106/DE/NIDCR NIH HHS/United States ; },
mesh = {Bacteria/classification/genetics/isolation & purification ; Computers ; *Databases, Genetic ; Genome, Bacterial ; Humans ; Internet ; Metagenome/*genetics ; Metagenomics ; Mouth/*microbiology ; Phenotype ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment ; Software ; },
abstract = {The human oral microbiome is the most studied human microflora, but 53% of the species have not yet been validly named and 35% remain uncultivated. The uncultivated taxa are known primarily from 16S rRNA sequence information. Sequence information tied solely to obscure isolate or clone numbers, and usually lacking accurate phylogenetic placement, is a major impediment to working with human oral microbiome data. The goal of creating the Human Oral Microbiome Database (HOMD) is to provide the scientific community with a body site-specific comprehensive database for the more than 600 prokaryote species that are present in the human oral cavity based on a curated 16S rRNA gene-based provisional naming scheme. Currently, two primary types of information are provided in HOMD--taxonomic and genomic. Named oral species and taxa identified from 16S rRNA gene sequence analysis of oral isolates and cloning studies were placed into defined 16S rRNA phylotypes and each given unique Human Oral Taxon (HOT) number. The HOT interlinks phenotypic, phylogenetic, genomic, clinical and bibliographic information for each taxon. A BLAST search tool is provided to match user 16S rRNA gene sequences to a curated, full length, 16S rRNA gene reference data set. For genomic analysis, HOMD provides comprehensive set of analysis tools and maintains frequently updated annotations for all the human oral microbial genomes that have been sequenced and publicly released. Oral bacterial genome sequences, determined as part of the Human Microbiome Project, are being added to the HOMD as they become available. We provide HOMD as a conceptual model for the presentation of microbiome data for other human body sites. Database URL: http://www.homd.org.},
}

Bacteria/classification/genetics/isolation & purification
Computers
*Databases, Genetic
Genome, Bacterial
Humans
Internet
Metagenome/*genetics
Metagenomics
Mouth/*microbiology
Phenotype
RNA, Bacterial/genetics
RNA, Ribosomal, 16S/genetics
Sequence Alignment
Software

@article {pmid20807838,
year = {2010},
author = {Sahota, G and Stormo, GD},
title = {Novel sequence-based method for identifying transcription factor binding sites in prokaryotic genomes.},
journal = {Bioinformatics (Oxford, England)},
volume = {26},
number = {21},
pages = {2672-2677},
pmid = {20807838},
issn = {1367-4811},
support = {T32 GM07200/GM/NIGMS NIH HHS/United States ; T32 GM008802/GM/NIGMS NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; R01 HG000249/HG/NHGRI NIH HHS/United States ; R01 HG00249/HG/NHGRI NIH HHS/United States ; },
mesh = {Binding Sites ; Computational Biology/methods ; *Genome ; *Promoter Regions, Genetic ; Sequence Analysis, DNA/*methods ; Transcription Factors/*chemistry/*metabolism ; },
abstract = {MOTIVATION: Computational techniques for microbial genomic sequence analysis are becoming increasingly important. With next-generation sequencing technology and the human microbiome project underway, current sequencing capacity is significantly greater than the speed at which organisms of interest can be studied experimentally. Most related computational work has been focused on sequence assembly, gene annotation and metabolic network reconstruction. We have developed a method that will primarily use available sequence data in order to determine prokaryotic transcription factor (TF) binding specificities.

RESULTS: Specificity determining residues (critical residues) were identified from crystal structures of DNA-protein complexes and TFs with the same critical residues were grouped into specificity classes. The putative binding regions for each class were defined as the set of promoters for each TF itself (autoregulatory) and the immediately upstream and downstream operons. MEME was used to find putative motifs within each separate class. Tests on the LacI and TetR TF families, using RegulonDB annotated sites, showed the sensitivity of prediction 86% and 80%, respectively.

AVAILABILITY: http://ural.wustl.edu/∼gsahota/HTHmotif/},
}

Binding Sites
Computational Biology/methods
*Genome
*Promoter Regions, Genetic
Sequence Analysis, DNA/*methods
Transcription Factors/*chemistry/*metabolism

@article {pmid20924228,
year = {2010},
author = {Foxman, B and Goldberg, D},
title = {Why the human microbiome project should motivate epidemiologists to learn ecology.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {21},
number = {6},
pages = {757-759},
pmid = {20924228},
issn = {1531-5487},
support = {R01 DE014899/DE/NIDCR NIH HHS/United States ; R01 HD038098/HD/NICHD NIH HHS/United States ; R01DE014899/DE/NIDCR NIH HHS/United States ; },
mesh = {*Ecology ; Epidemiology/*trends ; Humans ; *Metagenome ; Sequence Analysis, DNA ; },
}

*Ecology
Epidemiology/*trends
Humans
*Metagenome
Sequence Analysis, DNA

@article {pmid21133690,
year = {2010},
author = {Alauzet, C and Marchandin, H and Lozniewski, A},
title = {New insights into Prevotella diversity and medical microbiology.},
journal = {Future microbiology},
volume = {5},
number = {11},
pages = {1695-1718},
doi = {10.2217/fmb.10.126},
pmid = {21133690},
issn = {1746-0921},
mesh = {Bacteroidaceae Infections/*microbiology ; Drug Resistance, Bacterial ; *Genetic Variation ; Humans ; *Metagenome ; Prevotella/*classification/genetics/isolation & purification/*pathogenicity ; Virulence ; },
abstract = {In light of recent studies based on cultivation-independent methods, it appears that the diversity of Prevotella in human microbiota is greater than was previously assumed from cultivation-based studies, and that the implication of these bacteria in several human diseases was unrecognized. While some Prevotella taxa were found during opportunistic infections, changes in Prevotella abundance and diversity were discovered during dysbiosis-associated diseases. As member of the microbiota, Prevotella may also be considered as a reservoir for resistance genes. Greater knowledge on Prevotella diversity, as well as new insights into its pathogenic potential and implication in dysbiosis are expected from the use of human microbe identification microarrays, from whole-genome sequence analyse, and from the NIH Human Microbiome Project data. New approaches, including molecular-based methods, could contribute to improve the diagnosis of Prevotella infections.},
}

Bacteroidaceae Infections/*microbiology
Drug Resistance, Bacterial
*Genetic Variation
Humans
*Metagenome
Prevotella/*classification/genetics/isolation & purification/*pathogenicity
Virulence

@article {pmid21183674,
year = {2011},
author = {Cuív, PÓ and Klaassens, ES and Durkin, AS and Harkins, DM and Foster, L and McCorrison, J and Torralba, M and Nelson, KE and Morrison, M},
title = {Draft genome sequence of Turicibacter sanguinis PC909, isolated from human feces.},
journal = {Journal of bacteriology},
volume = {193},
number = {5},
pages = {1288-1289},
pmid = {21183674},
issn = {1098-5530},
mesh = {Feces/*microbiology ; *Genome, Bacterial ; Gram-Positive Bacteria/*genetics ; Humans ; Molecular Sequence Data ; },
abstract = {While the microbiota resident in the human gut is now known to provide a range of functions relevant to host health, many of the microbial members of the community have not yet been cultured or are represented by a limited number of isolates. We describe here the draft genome sequence of Turicibacter sanguinis PC909, isolated from a pooled healthy human fecal sample as part of the Australian Human Gut Microbiome Project.},
}

Feces/*microbiology
*Genome, Bacterial
Gram-Positive Bacteria/*genetics
Humans
Molecular Sequence Data

@article {pmid21304727,
year = {2010},
author = {Gilbert, JA and Meyer, F and Antonopoulos, D and Balaji, P and Brown, CT and Brown, CT and Desai, N and Eisen, JA and Evers, D and Field, D and Feng, W and Huson, D and Jansson, J and Knight, R and Knight, J and Kolker, E and Konstantindis, K and Kostka, J and Kyrpides, N and Mackelprang, R and McHardy, A and Quince, C and Raes, J and Sczyrba, A and Shade, A and Stevens, R},
title = {Meeting report: the terabase metagenomics workshop and the vision of an Earth microbiome project.},
journal = {Standards in genomic sciences},
volume = {3},
number = {3},
pages = {243-248},
pmid = {21304727},
issn = {1944-3277},
abstract = {Between July 18(th) and 24(th) 2010, 26 leading microbial ecology, computation, bioinformatics and statistics researchers came together in Snowbird, Utah (USA) to discuss the challenge of how to best characterize the microbial world using next-generation sequencing technologies. The meeting was entitled "Terabase Metagenomics" and was sponsored by the Institute for Computing in Science (ICiS) summer 2010 workshop program. The aim of the workshop was to explore the fundamental questions relating to microbial ecology that could be addressed using advances in sequencing potential. Technological advances in next-generation sequencing platforms such as the Illumina HiSeq 2000 can generate in excess of 250 billion base pairs of genetic information in 8 days. Thus, the generation of a trillion base pairs of genetic information is becoming a routine matter. The main outcome from this meeting was the birth of a concept and practical approach to exploring microbial life on earth, the Earth Microbiome Project (EMP). Here we briefly describe the highlights of this meeting and provide an overview of the EMP concept and how it can be applied to exploration of the microbiome of each ecosystem on this planet.},
}

@article {pmid21304728,
year = {2010},
author = {Gilbert, JA and Meyer, F and Jansson, J and Gordon, J and Pace, N and Tiedje, J and Ley, R and Fierer, N and Field, D and Kyrpides, N and Glöckner, FO and Klenk, HP and Wommack, KE and Glass, E and Docherty, K and Gallery, R and Stevens, R and Knight, R},
title = {The Earth Microbiome Project: Meeting report of the "1 EMP meeting on sample selection and acquisition" at Argonne National Laboratory October 6 2010.},
journal = {Standards in genomic sciences},
volume = {3},
number = {3},
pages = {249-253},
pmid = {21304728},
issn = {1944-3277},
abstract = {This report details the outcome the first meeting of the Earth Microbiome Project to discuss sample selection and acquisition. The meeting, held at the Argonne National Laboratory on Wednesday October 6(th) 2010, focused on discussion of how to prioritize environmental samples for sequencing and metagenomic analysis as part of the global effort of the EMP to systematically determine the functional and phylogenetic diversity of microbial communities across the world.},
}

@article {pmid21524302,
year = {2011},
author = {DeSantis, TZ and Keller, K and Karaoz, U and Alekseyenko, AV and Singh, NN and Brodie, EL and Pei, Z and Andersen, GL and Larsen, N},
title = {Simrank: Rapid and sensitive general-purpose k-mer search tool.},
journal = {BMC ecology},
volume = {11},
number = {},
pages = {11},
pmid = {21524302},
issn = {1472-6785},
support = {AI075410-01/AI/NIAID NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; UH2/UH3CA140233/CA/NCI NIH HHS/United States ; },
mesh = {Computational Biology ; DNA ; *Databases, Bibliographic ; *Databases, Factual ; *Molecular Biology ; Proteins ; RNA ; *Software ; },
abstract = {BACKGROUND: Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project http://nihroadmap.nih.gov/hmp. Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available.

RESULTS: Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset.

CONCLUSIONS: Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity.},
}

Computational Biology
DNA
*Databases, Bibliographic
*Databases, Factual
*Molecular Biology
Proteins
RNA
*Software

@article {pmid21540692,
year = {2011},
author = {Gregory, KE},
title = {Microbiome aspects of perinatal and neonatal health.},
journal = {The Journal of perinatal & neonatal nursing},
volume = {25},
number = {2},
pages = {158-62; quiz 163-4},
pmid = {21540692},
issn = {1550-5073},
support = {K23 NR011320/NR/NINR NIH HHS/United States ; },
mesh = {DNA, Bacterial ; Female ; Genes, Bacterial ; Gram-Negative Bacteria/genetics ; Gram-Positive Bacteria/genetics ; Humans ; *Infant Welfare ; Infant, Newborn ; Infant, Newborn, Diseases/*microbiology ; Male ; *Maternal Welfare ; Metagenome/*physiology ; Nursing Research ; Perinatal Care ; Pregnancy ; Sensitivity and Specificity ; },
abstract = {Our human cells are outnumbered 10 to 1 by bacterial cells. For this reason, the role of microorganisms, specifically bacteria, in health and disease has brought forth intense research via the Human Microbiome Project. The Human Microbiome Project is a National Institutes of Health sponsored effort to build upon the Human Genome Project in understanding human genetic and physiologic diversity. Perinatal and neonatal health represents areas of high importance for knowledge generated by the Human Microbiome Project as the microbiome is largely influenced during pregnancy, birth, and the neonatal period by nutrition, lifestyle, environmental factors of care, and the administration of medications, specifically antibiotics. As nurses have a depth of expertise in these areas, they will make a significant contribution toward better understanding the role of the microbiome in disease, and how to manipulate the microbiome to advantage patients toward health. This article describes the human microbiome and why it is important to overall health and disease. Three major unsolved problems in perinatal and neonatal health including (1) preterm birth; (2) the neonatal consequences of vaginal versus cesarean birth; and (3) neonatal gastrointestinal disease, specifically, necrotizing enterocolitis, are discussed in the context of current and future research on the human microbiome.},
}

DNA, Bacterial
Female
Genes, Bacterial
Gram-Negative Bacteria/genetics
Gram-Positive Bacteria/genetics
Humans
*Infant Welfare
Infant, Newborn
Infant, Newborn, Diseases/*microbiology
Male
*Maternal Welfare
Metagenome/*physiology
Nursing Research
Perinatal Care
Pregnancy
Sensitivity and Specificity

@article {pmid21559529,
year = {2011},
author = {Saulnier, DM and Santos, F and Roos, S and Mistretta, TA and Spinler, JK and Molenaar, D and Teusink, B and Versalovic, J},
title = {Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features.},
journal = {PloS one},
volume = {6},
number = {4},
pages = {e18783},
pmid = {21559529},
issn = {1932-6203},
support = {P30 DK56338/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; },
mesh = {Bacterial Adhesion ; Biofilms ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Humans ; Limosilactobacillus reuteri/*genetics ; Metabolic Networks and Pathways/genetics ; Milk, Human/microbiology ; Multigene Family ; Polysaccharides/chemistry ; Probiotics/*metabolism ; Species Specificity ; Transcriptome ; },
abstract = {The genomes of four Lactobacillus reuteri strains isolated from human breast milk and the gastrointestinal tract have been recently sequenced as part of the Human Microbiome Project. Preliminary genome comparisons suggested that these strains belong to two different clades, previously shown to differ with respect to antimicrobial production, biofilm formation, and immunomodulation. To explain possible mechanisms of survival in the host and probiosis, we completed a detailed genomic comparison of two breast milk-derived isolates representative of each group: an established probiotic strain (L. reuteri ATCC 55730) and a strain with promising probiotic features (L. reuteri ATCC PTA 6475). Transcriptomes of L. reuteri strains in different growth phases were monitored using strain-specific microarrays, and compared using a pan-metabolic model representing all known metabolic reactions present in these strains. Both strains contained candidate genes involved in the survival and persistence in the gut such as mucus-binding proteins and enzymes scavenging reactive oxygen species. A large operon predicted to encode the synthesis of an exopolysaccharide was identified in strain 55730. Both strains were predicted to produce health-promoting factors, including antimicrobial agents and vitamins (folate, vitamin B(12)). Additionally, a complete pathway for thiamine biosynthesis was predicted in strain 55730 for the first time in this species. Candidate genes responsible for immunomodulatory properties of each strain were identified by transcriptomic comparisons. The production of bioactive metabolites by human-derived probiotics may be predicted using metabolic modeling and transcriptomics. Such strategies may facilitate selection and optimization of probiotics for health promotion, disease prevention and amelioration.},
}

Bacterial Adhesion
Biofilms
Gene Expression Profiling
*Gene Expression Regulation, Bacterial
*Genome, Bacterial
Humans
Limosilactobacillus reuteri/*genetics
Metabolic Networks and Pathways/genetics
Milk, Human/microbiology
Multigene Family
Polysaccharides/chemistry
Probiotics/*metabolism
Species Specificity
Transcriptome

@article {pmid21726221,
year = {2011},
author = {Peterson, SN and Snesrud, E and Schork, NJ and Bretz, WA},
title = {Dental caries pathogenicity: a genomic and metagenomic perspective.},
journal = {International dental journal},
volume = {61 Suppl 1},
number = {Suppl 1},
pages = {11-22},
pmid = {21726221},
issn = {0020-6539},
support = {R01 DE015351/DE/NIDCR NIH HHS/United States ; },
mesh = {Animals ; *Biofilms ; Dental Caries/*genetics/*microbiology ; Dental Plaque/genetics/microbiology ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genomics ; Glycolysis ; Humans ; Metagenome ; Microbial Interactions ; Streptococcus mutans/genetics/metabolism ; },
abstract = {In this review we address the subject of dental caries pathogenicity from a genomic and metagenomic perspective. The application of genomic technologies is certain to yield novel insights into the relationship between the bacterial flora, dental health and disease. Three primary attributes of bacterial species are thought to have direct impact on caries development, these include: adherence on tooth surfaces (biofilm formation), acid production and acid tolerance. Attempts to define the specific aetiological agents of dental caries have proven to be elusive, supporting the notion that caries aetiology is perhaps complex and multi-faceted. The recently introduced Human Microbiome Project (HMP) that endeavors to characterise the micro-organisms living in and on the human body is likely to shed new light on these questions and improve our understanding of polymicrobial disease, microbial ecology in the oral cavity and provide new avenues for therapeutic and molecular diagnostics developments.},
}

Animals
*Biofilms
Dental Caries/*genetics/*microbiology
Dental Plaque/genetics/microbiology
Gene Expression Profiling
*Gene Expression Regulation, Bacterial
*Genomics
Glycolysis
Humans
Metagenome
Microbial Interactions
Streptococcus mutans/genetics/metabolism

@article {pmid21729521,
year = {2011},
author = {Wu, KF and Zheng, GG and Ma, XT and Song, YH and Zhu, XF},
title = {[Mechanism of leukemia relapse: novel insights on old problem].},
journal = {Zhongguo shi yan xue ye xue za zhi},
volume = {19},
number = {3},
pages = {557-560},
pmid = {21729521},
issn = {1009-2137},
mesh = {Cell Fusion ; Humans ; Leukemia/*pathology ; Neoplasm, Residual/pathology ; Recurrence ; },
abstract = {Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials.},
}

Cell Fusion
Humans
Leukemia/*pathology
Neoplasm, Residual/pathology
Recurrence

@article {pmid21772835,
year = {2011},
author = {Young, VB and Kahn, SA and Schmidt, TM and Chang, EB},
title = {Studying the Enteric Microbiome in Inflammatory Bowel Diseases: Getting through the Growing Pains and Moving Forward.},
journal = {Frontiers in microbiology},
volume = {2},
number = {},
pages = {144},
pmid = {21772835},
issn = {1664-302X},
support = {UH3 DK083993/DK/NIDDK NIH HHS/United States ; },
abstract = {In this commentary, we will review some of the early efforts aimed at understanding the role of the enteric microbiota in the causality of inflammatory bowel diseases. By examining these studies and drawing on our own experiences bridging clinical gastroenterology and microbial ecology as part of the NIH-funded Human Microbiome Project (Turnbaugh et al., 2007), we hope to help define some of the "growing pains" that have hampered these initial efforts. It is our sincere hope that this discussion will help advance future efforts in this area by identifying current challenges and limitations and by suggesting strategies to overcome these obstacles.},
}

@article {pmid22018227,
year = {2011},
author = {Proctor, LM},
title = {The Human Microbiome Project in 2011 and beyond.},
journal = {Cell host & microbe},
volume = {10},
number = {4},
pages = {287-291},
doi = {10.1016/j.chom.2011.10.001},
pmid = {22018227},
issn = {1934-6069},
mesh = {*Biodiversity ; Humans ; *Metagenome ; },
abstract = {The human microbiome comprises the genes and genomes of the microbiota that inhabit the body. We highlight Human Microbiome Project (HMP) resources, including 600 microbial reference genomes, 70 million 16S sequences, 700 metagenomes, and 60 million predicted genes from healthy adult microbiomes. Microbiome studies of specific diseases and future research directions are also discussed.},
}

*Biodiversity
Humans
*Metagenome

@article {pmid22112388,
year = {2012},
author = {Lewis, CM and Obregón-Tito, A and Tito, RY and Foster, MW and Spicer, PG},
title = {The Human Microbiome Project: lessons from human genomics.},
journal = {Trends in microbiology},
volume = {20},
number = {1},
pages = {1-4},
pmid = {22112388},
issn = {1878-4380},
support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; R01 HG005172-01/HG/NHGRI NIH HHS/United States ; R01 GM089886-01A1/GM/NIGMS NIH HHS/United States ; },
mesh = {Genomics/*methods/trends ; Humans ; Medicine/methods/trends ; *Metagenome ; },
abstract = {The Human Microbiome Project (HMP) is following in the footsteps of the Human Genome Project (HGP), which will include exciting discoveries, but also potential disappointment and resentment over the lack of medical applications. There is a wiser path for the HMP. This path includes a greater attention to rare variation, an early commitment to an ethical inclusion of indigenous communities, and a recruitment strategy in which medical benefits are de-emphasized.},
}

Genomics/*methods/trends
Humans
Medicine/methods/trends
*Metagenome

@article {pmid22134646,
year = {2012},
author = {McDonald, D and Price, MN and Goodrich, J and Nawrocki, EP and DeSantis, TZ and Probst, A and Andersen, GL and Knight, R and Hugenholtz, P},
title = {An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea.},
journal = {The ISME journal},
volume = {6},
number = {3},
pages = {610-618},
pmid = {22134646},
issn = {1751-7370},
support = {UH2/UH3CA140233/CA/NCI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; },
mesh = {Archaea/*classification/genetics ; Bacteria/*classification/genetics ; Classification/*methods ; *Databases, Genetic ; Metagenomics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Software ; },
abstract = {Reference phylogenies are crucial for providing a taxonomic framework for interpretation of marker gene and metagenomic surveys, which continue to reveal novel species at a remarkable rate. Greengenes is a dedicated full-length 16S rRNA gene database that provides users with a curated taxonomy based on de novo tree inference. We developed a 'taxonomy to tree' approach for transferring group names from an existing taxonomy to a tree topology, and used it to apply the Greengenes, National Center for Biotechnology Information (NCBI) and cyanoDB (Cyanobacteria only) taxonomies to a de novo tree comprising 408,315 sequences. We also incorporated explicit rank information provided by the NCBI taxonomy to group names (by prefixing rank designations) for better user orientation and classification consistency. The resulting merged taxonomy improved the classification of 75% of the sequences by one or more ranks relative to the original NCBI taxonomy with the most pronounced improvements occurring in under-classified environmental sequences. We also assessed candidate phyla (divisions) currently defined by NCBI and present recommendations for consolidation of 34 redundantly named groups. All intermediate results from the pipeline, which includes tree inference, jackknifing and transfer of a donor taxonomy to a recipient tree (tax2tree) are available for download. The improved Greengenes taxonomy should provide important infrastructure for a wide range of megasequencing projects studying ecosystems on scales ranging from our own bodies (the Human Microbiome Project) to the entire planet (the Earth Microbiome Project). The implementation of the software can be obtained from http://sourceforge.net/projects/tax2tree/.},
}

Archaea/*classification/genetics
Bacteria/*classification/genetics
Classification/*methods
*Databases, Genetic
Metagenomics
*Phylogeny
RNA, Ribosomal, 16S/genetics
Software

@article {pmid22194640,
year = {2012},
author = {Markowitz, VM and Chen, IM and Palaniappan, K and Chu, K and Szeto, E and Grechkin, Y and Ratner, A and Jacob, B and Huang, J and Williams, P and Huntemann, M and Anderson, I and Mavromatis, K and Ivanova, NN and Kyrpides, NC},
title = {IMG: the Integrated Microbial Genomes database and comparative analysis system.},
journal = {Nucleic acids research},
volume = {40},
number = {Database issue},
pages = {D115-22},
pmid = {22194640},
issn = {1362-4962},
support = {U01-HG004866/HG/NHGRI NIH HHS/United States ; },
mesh = {*Databases, Genetic ; Eukaryota/genetics ; *Genome, Archaeal ; *Genome, Bacterial ; *Genome, Viral ; *Genomics ; Phenotype ; Plasmids/genetics ; Proteomics ; Software ; Systems Integration ; },
abstract = {The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp).},
}

*Databases, Genetic
Eukaryota/genetics
*Genome, Archaeal
*Genome, Bacterial
*Genome, Viral
*Genomics
Phenotype
Plasmids/genetics
Proteomics
Software
Systems Integration

@article {pmid22209085,
year = {2012},
author = {Rath, CM and Dorrestein, PC},
title = {The bacterial chemical repertoire mediates metabolic exchange within gut microbiomes.},
journal = {Current opinion in microbiology},
volume = {15},
number = {2},
pages = {147-154},
pmid = {22209085},
issn = {1879-0364},
support = {R01 GM094802/GM/NIGMS NIH HHS/United States ; R01 GM086283/GM/NIGMS NIH HHS/United States ; GM094802/GM/NIGMS NIH HHS/United States ; AI095125/AI/NIAID NIH HHS/United States ; R01 AI095125/AI/NIAID NIH HHS/United States ; GM086283/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Bacteria/*chemistry/classification/growth & development/*metabolism ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Mice ; *Microbial Interactions ; Phenotype ; },
abstract = {Microbial communities in the gut have been hypothesized to play key roles in the health of the host organism. Exploring the relationship between these populations and disease states has been a focus of the human microbiome project. However, the biological roles of the compounds produced by the gut bacteria are largely unknown. We hypothesize that these compounds act as metabolic exchange factors-mediating inter-species and intra-species interactions in the microbiome. This view is supported through this review of known bacterial metabolic exchange factors and evidence for uncharacterized metabolic exchange factors in the gut. The impact of model systems and technological developments in exploring this hypothesis are also discussed. Together, these investigations are revolutionizing our understanding of the gut microbiome-presenting the possibility of identifying new strategies for treating disease in the host.},
}

Animals
Bacteria/*chemistry/classification/growth & development/*metabolism
Gastrointestinal Tract/*microbiology
Humans
*Metagenome
Mice
*Microbial Interactions
Phenotype

@article {pmid22237180,
year = {2012},
author = {Baig, S},
title = {Reviewing personal bacteria - the human microbiome project.},
journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP},
volume = {22},
number = {1},
pages = {3-4},
pmid = {22237180},
issn = {1681-7168},
mesh = {Bacteria/*genetics ; Bacterial Infections/*microbiology ; *Biomedical Research ; Female ; Humans ; Male ; *Metagenome ; },
}

Bacteria/*genetics
Bacterial Infections/*microbiology
*Biomedical Research
Female
Humans
Male
*Metagenome

@article {pmid22574119,
year = {2012},
author = {Sanchez, LM and Wong, WR and Riener, RM and Schulze, CJ and Linington, RG},
title = {Examining the fish microbiome: vertebrate-derived bacteria as an environmental niche for the discovery of unique marine natural products.},
journal = {PloS one},
volume = {7},
number = {5},
pages = {e35398},
pmid = {22574119},
issn = {1932-6203},
support = {U01 TW006634/TW/FIC NIH HHS/United States ; 2R25GM05803-12/GM/NIGMS NIH HHS/United States ; TW006634/TW/FIC NIH HHS/United States ; },
mesh = {Animals ; Bacteria/classification/growth & development/*isolation & purification/*metabolism ; Biodiversity ; Biological Products/*metabolism ; Culture Techniques ; *Drug Discovery ; Fishes/*microbiology ; Intestines/microbiology ; *Metagenome ; Oceans and Seas ; Phylogeny ; },
abstract = {Historically, marine invertebrates have been a prolific source of unique natural products, with a diverse array of biological activities. Recent studies of invertebrate-associated microbial communities are revealing microorganisms as the true producers of many of these compounds. Inspired by the human microbiome project, which has highlighted the human intestine as a unique microenvironment in terms of microbial diversity, we elected to examine the bacterial communities of fish intestines (which we have termed the fish microbiome) as a new source of microbial and biosynthetic diversity for natural products discovery. To test the hypothesis that the fish microbiome contains microorganisms with unique capacity for biosynthesizing natural products, we examined six species of fish through a combination of dissection and culture-dependent evaluation of intestinal microbial communities. Using isolation media designed to enrich for marine Actinobacteria, we have found three main clades that show taxonomic divergence from known strains, several of which are previously uncultured. Extracts from these strains exhibit a wide range of activities against both gram-positive and gram-negative human pathogens, as well as several fish pathogens. Exploration of one of these extracts has identified the novel bioactive lipid sebastenoic acid as an anti-microbial agent, with activity against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecium, and Vibrio mimicus.},
}

Animals
Bacteria/classification/growth & development/*isolation & purification/*metabolism
Biodiversity
Biological Products/*metabolism
Culture Techniques
*Drug Discovery
Fishes/*microbiology
Intestines/microbiology
*Metagenome
Oceans and Seas
Phylogeny

@article {pmid22577297,
year = {2012},
author = {Liu, Z and Bensmail, H and Tan, M},
title = {Efficient feature selection and multiclass classification with integrated instance and model based learning.},
journal = {Evolutionary bioinformatics online},
volume = {8},
number = {},
pages = {197-205},
pmid = {22577297},
issn = {1176-9343},
support = {R03 CA133899/CA/NCI NIH HHS/United States ; },
abstract = {Multiclass classification and feature (variable) selections are commonly encountered in many biological and medical applications. However, extending binary classification approaches to multiclass problems is not trivial. Instance-based methods such as the K nearest neighbor (KNN) can naturally extend to multiclass problems and usually perform well with unbalanced data, but suffer from the curse of dimensionality. Their performance is degraded when applied to high dimensional data. On the other hand, model-based methods such as logistic regression require the decomposition of the multiclass problem into several binary problems with one-vs.-one or one-vs.-rest schemes. Even though they can be applied to high dimensional data with L(1) or L(p) penalized methods, such approaches can only select independent features and the features selected with different binary problems are usually different. They also produce unbalanced classification problems with one vs. the rest scheme even if the original multiclass problem is balanced.By combining instance-based and model-based learning, we propose an efficient learning method with integrated KNN and constrained logistic regression (KNNLog) for simultaneous multiclass classification and feature selection. Our proposed method simultaneously minimizes the intra-class distance and maximizes the interclass distance with fewer estimated parameters. It is very efficient for problems with small sample size and unbalanced classes, a case common in many real applications. In addition, our model-based feature selection methods can identify highly correlated features simultaneously avoiding the multiplicity problem due to multiple tests. The proposed method is evaluated with simulation and real data including one unbalanced microRNA dataset for leukemia and one multiclass metagenomic dataset from the Human Microbiome Project (HMP). It performs well with limited computational experiments.},
}

@article {pmid22635997,
year = {2012},
author = {Wu, YW and Rho, M and Doak, TG and Ye, Y},
title = {Oral spirochetes implicated in dental diseases are widespread in normal human subjects and carry extremely diverse integron gene cassettes.},
journal = {Applied and environmental microbiology},
volume = {78},
number = {15},
pages = {5288-5296},
pmid = {22635997},
issn = {1098-5336},
mesh = {Base Pairing ; Base Sequence ; Cluster Analysis ; Computational Biology/*methods ; Computer Simulation ; DNA Primers/genetics ; Humans ; Integrons/*genetics ; Metagenome/*genetics ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Stomatognathic Diseases/*microbiology ; Treponema/*genetics ; },
abstract = {The NIH Human Microbiome Project (HMP) has produced several hundred metagenomic data sets, allowing studies of the many functional elements in human-associated microbial communities. Here, we survey the distribution of oral spirochetes implicated in dental diseases in normal human individuals, using recombination sites associated with the chromosomal integron in Treponema genomes, taking advantage of the multiple copies of the integron recombination sites (repeats) in the genomes, and using a targeted assembly approach that we have developed. We find that integron-containing Treponema species are present in ∼80% of the normal human subjects included in the HMP. Further, we are able to de novo assemble the integron gene cassettes using our constrained assembly approach, which employs a unique application of the de Bruijn graph assembly information; most of these cassette genes were not assembled in whole-metagenome assemblies and could not be identified by mapping sequencing reads onto the known reference Treponema genomes due to the dynamic nature of integron gene cassettes. Our study significantly enriches the gene pool known to be carried by Treponema chromosomal integrons, totaling 826 (598 97% nonredundant) genes. We characterize the functions of these gene cassettes: many of these genes have unknown functions. The integron gene cassette arrays found in the human microbiome are extraordinarily dynamic, with different microbial communities sharing only a small number of common genes.},
}

Base Pairing
Base Sequence
Cluster Analysis
Computational Biology/*methods
Computer Simulation
DNA Primers/genetics
Humans
Integrons/*genetics
Metagenome/*genetics
Molecular Sequence Data
Phylogeny
Polymerase Chain Reaction
Stomatognathic Diseases/*microbiology
Treponema/*genetics

@article {pmid22675588,
year = {2011},
author = {Earl, AM and Desjardins, CA and Fitzgerald, MG and Arachchi, HM and Zeng, Q and Mehta, T and Griggs, A and Birren, BW and Toney, NC and Carr, J and Posey, J and Butler, WR},
title = {High quality draft genome sequence of Segniliparus rugosus CDC 945(T)= (ATCC BAA-974(T)).},
journal = {Standards in genomic sciences},
volume = {5},
number = {3},
pages = {389-397},
pmid = {22675588},
issn = {1944-3277},
support = {HHSN272200900017C/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; },
abstract = {Segniliparus rugosus represents one of two species in the genus Segniliparus, the sole genus in the family Segniliparaceae. A unique and interesting feature of this family is the presence of extremely long carbon-chain length mycolic acids bound in the cell wall. S. rugosus is also a medically important species because it is an opportunistic pathogen associated with mammalian lung disease. This report represents the second species in the genus to have its genome sequenced. The 3,567,567 bp long genome with 3,516 protein-coding and 49 RNA genes is part of the NIH Roadmap for Medical Research, Human Microbiome Project.},
}

@article {pmid22683238,
year = {2012},
author = {Dave, M and Higgins, PD and Middha, S and Rioux, KP},
title = {The human gut microbiome: current knowledge, challenges, and future directions.},
journal = {Translational research : the journal of laboratory and clinical medicine},
volume = {160},
number = {4},
pages = {246-257},
doi = {10.1016/j.trsl.2012.05.003},
pmid = {22683238},
issn = {1878-1810},
mesh = {Adaptive Immunity/physiology ; Bacteria/*classification ; Computational Biology ; Gastrointestinal Tract/*microbiology ; Humans ; Immunity, Innate/physiology ; },
abstract = {The Human Genome Project was completed a decade ago, leaving a legacy of process, tools, and infrastructure now being turned to the study of the microbes that reside in and on the human body as determinants of health and disease, and has been branded "The Human Microbiome Project." Of the various niches under investigation, the human gut houses the most complex and abundant microbial community and is an arena for important host-microbial interactions that have both local and systemic impact. Initial studies of the human microbiome have been largely descriptive, a testing ground for innovative molecular techniques and new hypotheses. Methods for studying the microbiome have quickly evolved from low-resolution surveys of microbial community structure to high-definition description of composition, function, and ecology. Next-generation sequencing technologies combined with advanced bioinformatics place us at the doorstep of revolutionary insight into the composition, capability, and activity of the human intestinal microbiome. Renewed efforts to cultivate previously "uncultivable" microbes will be important to the overall understanding of gut ecology. There remain numerous methodological challenges to the effective study and understanding of the gut microbiome, largely relating to study design, sample collection, and the number of predictor variables. Strategic collaboration of clinicians, microbiologists, molecular biologists, computational scientists, and bioinformaticians is the ideal paradigm for success in this field. Meaningful interpretation of the gut microbiome requires that host genetic and environmental influences be controlled or accounted for. Understanding the gut microbiome in healthy humans is a foundation for discovering its influence in various important gastrointestinal and nutritional diseases (eg, inflammatory bowel disease, diabetes, and obesity), and for rational translation to human health gains.},
}

Adaptive Immunity/physiology
Bacteria/*classification
Computational Biology
Gastrointestinal Tract/*microbiology
Humans
Immunity, Innate/physiology

@article {pmid22698087,
year = {2012},
author = {Segata, N and Haake, SK and Mannon, P and Lemon, KP and Waldron, L and Gevers, D and Huttenhower, C and Izard, J},
title = {Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples.},
journal = {Genome biology},
volume = {13},
number = {6},
pages = {R42},
pmid = {22698087},
issn = {1474-760X},
support = {HG004969/HG/NHGRI NIH HHS/United States ; DE020751/DE/NIDCR NIH HHS/United States ; HG005969/HG/NHGRI NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; DE020298/DE/NIDCR NIH HHS/United States ; DE021574/DE/NIDCR NIH HHS/United States ; },
mesh = {Actinobacteria/classification/genetics/isolation & purification ; Adolescent ; Adult ; Bacterial Typing Techniques/methods ; Bacteroidetes/classification/genetics/isolation & purification ; *Biota ; Feces/*microbiology ; Female ; Genes, rRNA ; Humans ; Male ; *Metagenome ; Mouth/*microbiology ; Palatine Tonsil/*microbiology ; Pharynx/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/analysis/genetics ; Saliva/microbiology ; Veillonellaceae/classification/genetics/isolation & purification ; Young Adult ; },
abstract = {BACKGROUND: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body's greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

RESULTS: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; and stool. Phyla initially identified from environmental samples were detected throughout this population, primarily TM7, SR1, and Synergistetes. Genera with pathogenic members were well-represented among this disease-free cohort. Tooth-associated communities were distinct, but not entirely dissimilar, from other oral surfaces. The Porphyromonadaceae, Veillonellaceae and Lachnospiraceae families were common to all sites, but the distributions of their genera varied significantly. Most metabolic processes were distributed widely throughout the digestive tract microbiota, with variations in metagenomic abundance between body habitats. These included shifts in sugar transporter types between the supragingival plaque, other oral surfaces, and stool; hydrogen and hydrogen sulfide production were also differentially distributed.

CONCLUSIONS: The microbiomes of ten digestive tract sites separated into four types based on composition. A core set of metabolic pathways was present across these diverse digestive tract habitats. These data provide a critical baseline for future studies investigating local and systemic diseases affecting human health.},
}

Actinobacteria/classification/genetics/isolation & purification
Adolescent
Adult
Bacterial Typing Techniques/methods
Bacteroidetes/classification/genetics/isolation & purification
*Biota
Feces/*microbiology
Female
Genes, rRNA
Humans
Male
*Metagenome
Mouth/*microbiology
Palatine Tonsil/*microbiology
Pharynx/*microbiology
Phylogeny
RNA, Ribosomal, 16S/analysis/genetics
Saliva/microbiology
Veillonellaceae/classification/genetics/isolation & purification
Young Adult

@article {pmid22699609,
year = {2012},
author = {, },
title = {Structure, function and diversity of the healthy human microbiome.},
journal = {Nature},
volume = {486},
number = {7402},
pages = {207-214},
pmid = {22699609},
issn = {1476-4687},
support = {R01HG004856/HG/NHGRI NIH HHS/United States ; R01HG004908/HG/NHGRI NIH HHS/United States ; P30DE020751/DE/NIDCR NIH HHS/United States ; R21HG005811/HG/NHGRI NIH HHS/United States ; R01HG005172/HG/NHGRI NIH HHS/United States ; UH3DK083993/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01HG004900/HG/NHGRI NIH HHS/United States ; UH2 DK083990/DK/NIDDK NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U01DE016937/DE/NIDCR NIH HHS/United States ; UH2 AR057504/AR/NIAMS NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; R01HG004877/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; DP2OD001500/OD/NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; R01 HG004856/HG/NHGRI NIH HHS/United States ; R01 HG005171/HG/NHGRI NIH HHS/United States ; UH3AI083263/AI/NIAID NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; UH2AR057504/AR/NIAMS NIH HHS/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; UH3AR057504/AR/NIAMS NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; UH2AI083263/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; R01DE021574/DE/NIDCR NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; R01HG004857/HG/NHGRI NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; R01HG005171/HG/NHGRI NIH HHS/United States ; T32AI007528/AI/NIAID NIH HHS/United States ; R01HG004906/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; R01 DE021574/DE/NIDCR NIH HHS/United States ; RC1 DE020298/DE/NIDCR NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21CA139193/CA/NCI NIH HHS/United States ; R21 HG005811/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; R01 HG004853/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; UH2DK083990/DK/NIDDK NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; RC1DE0202098/DE/NIDCR NIH HHS/United States ; R01 HG004906/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG004877/HG/NHGRI NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; UH2AR057506/AR/NIAMS NIH HHS/United States ; N01 AI030071/AI/NIAID NIH HHS/United States ; N01 HG062088/HG/NHGRI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Bacteria/*classification/genetics ; *Biodiversity ; Ecosystem ; Female ; *Health ; Humans ; Male ; Metabolic Networks and Pathways/physiology ; *Metagenome ; Metagenomics ; Phenotype ; RNA, Ribosomal, 16S/genetics ; Young Adult ; },
abstract = {Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.},
}

Adolescent
Adult
Bacteria/*classification/genetics
*Biodiversity
Ecosystem
Female
*Health
Humans
Male
Metabolic Networks and Pathways/physiology
*Metagenome
Metagenomics
Phenotype
RNA, Ribosomal, 16S/genetics
Young Adult

@article {pmid22699610,
year = {2012},
author = {, },
title = {A framework for human microbiome research.},
journal = {Nature},
volume = {486},
number = {7402},
pages = {215-221},
pmid = {22699610},
issn = {1476-4687},
support = {R01HG004856/HG/NHGRI NIH HHS/United States ; R01HG004908/HG/NHGRI NIH HHS/United States ; P30DE020751/DE/NIDCR NIH HHS/United States ; R21HG005811/HG/NHGRI NIH HHS/United States ; R01HG005172/HG/NHGRI NIH HHS/United States ; UH3DK083993/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01HG004900/HG/NHGRI NIH HHS/United States ; UH2 DK083990/DK/NIDDK NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U01DE016937/DE/NIDCR NIH HHS/United States ; RC1DE020298/DE/NIDCR NIH HHS/United States ; UH2 AR057504/AR/NIAMS NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; R01HG004877/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; DP2OD001500/OD/NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; R01 HG004856/HG/NHGRI NIH HHS/United States ; R01 HG005171/HG/NHGRI NIH HHS/United States ; UH3AI083263/AI/NIAID NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; UH2AR057504/AR/NIAMS NIH HHS/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; UH3AR057504/AR/NIAMS NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; UH2AI083263/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; R01DE021574/DE/NIDCR NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; R01HG005171/HG/NHGRI NIH HHS/United States ; T32AI007528/AI/NIAID NIH HHS/United States ; R01HG004906/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; R01 DE021574/DE/NIDCR NIH HHS/United States ; RC1 DE020298/DE/NIDCR NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21CA139193/CA/NCI NIH HHS/United States ; R21 HG005811/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; R01 HG004853/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG00485/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; UH2DK083990/DK/NIDDK NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; R01 HG004906/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG004877/HG/NHGRI NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; UH2AR057506/AR/NIAMS NIH HHS/United States ; N01 AI030071/AI/NIAID NIH HHS/United States ; N01 HG062088/HG/NHGRI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Bacteria/*genetics ; Female ; Humans ; Male ; *Metagenome ; Metagenomics/*methods ; RNA, Ribosomal, 16S/genetics ; Reference Standards ; Statistics as Topic ; Young Adult ; },
abstract = {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.},
}

Adolescent
Adult
Bacteria/*genetics
Female
Humans
Male
*Metagenome
Metagenomics/*methods
RNA, Ribosomal, 16S/genetics
Reference Standards
Statistics as Topic
Young Adult

@article {pmid22719234,
year = {2012},
author = {Abubucker, S and Segata, N and Goll, J and Schubert, AM and Izard, J and Cantarel, BL and Rodriguez-Mueller, B and Zucker, J and Thiagarajan, M and Henrissat, B and White, O and Kelley, ST and Methé, B and Schloss, PD and Gevers, D and Mitreva, M and Huttenhower, C},
title = {Metabolic reconstruction for metagenomic data and its application to the human microbiome.},
journal = {PLoS computational biology},
volume = {8},
number = {6},
pages = {e1002358},
pmid = {22719234},
issn = {1553-7358},
support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; R21 DE017106/DE/NIDCR NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; 5R01HG005975/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; DE017106/DE/NIDCR NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; },
mesh = {Computational Biology ; Digestive System/metabolism/microbiology ; Female ; Genetics, Microbial ; Glycosaminoglycans/metabolism ; Humans ; Hydrogen-Ion Concentration ; Metabolic Networks and Pathways/genetics ; Metabolome/genetics ; *Metagenome ; Multigene Family ; Vagina/metabolism/microbiology ; },
abstract = {Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/humann. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future metagenomic studies.},
}

Computational Biology
Digestive System/metabolism/microbiology
Female
Genetics, Microbial
Glycosaminoglycans/metabolism
Humans
Hydrogen-Ion Concentration
Metabolic Networks and Pathways/genetics
Metabolome/genetics
*Metagenome
Multigene Family
Vagina/metabolism/microbiology

@article {pmid22719260,
year = {2012},
author = {Rho, M and Wu, YW and Tang, H and Doak, TG and Ye, Y},
title = {Diverse CRISPRs evolving in human microbiomes.},
journal = {PLoS genetics},
volume = {8},
number = {6},
pages = {e1002441},
pmid = {22719260},
issn = {1553-7404},
support = {R01 HG004908/HG/NHGRI NIH HHS/United States ; 1R01HG004908/HG/NHGRI NIH HHS/United States ; },
mesh = {Archaea/genetics ; Bacteria/genetics/virology ; Bacteriophages/genetics ; Base Sequence ; DNA, Intergenic/*genetics ; *Evolution, Molecular ; Genome, Bacterial ; Humans ; Inverted Repeat Sequences/*genetics ; Metagenome/*genetics ; Metagenomics ; Molecular Sequence Data ; Plasmids/genetics ; Sequence Analysis, DNA ; Streptococcus/genetics/virology ; },
abstract = {CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci, together with cas (CRISPR-associated) genes, form the CRISPR/Cas adaptive immune system, a primary defense strategy that eubacteria and archaea mobilize against foreign nucleic acids, including phages and conjugative plasmids. Short spacer sequences separated by the repeats are derived from foreign DNA and direct interference to future infections. The availability of hundreds of shotgun metagenomic datasets from the Human Microbiome Project (HMP) enables us to explore the distribution and diversity of known CRISPRs in human-associated microbial communities and to discover new CRISPRs. We propose a targeted assembly strategy to reconstruct CRISPR arrays, which whole-metagenome assemblies fail to identify. For each known CRISPR type (identified from reference genomes), we use its direct repeat consensus sequence to recruit reads from each HMP dataset and then assemble the recruited reads into CRISPR loci; the unique spacer sequences can then be extracted for analysis. We also identified novel CRISPRs or new CRISPR variants in contigs from whole-metagenome assemblies and used targeted assembly to more comprehensively identify these CRISPRs across samples. We observed that the distributions of CRISPRs (including 64 known and 86 novel ones) are largely body-site specific. We provide detailed analysis of several CRISPR loci, including novel CRISPRs. For example, known streptococcal CRISPRs were identified in most oral microbiomes, totaling ∼8,000 unique spacers: samples resampled from the same individual and oral site shared the most spacers; different oral sites from the same individual shared significantly fewer, while different individuals had almost no common spacers, indicating the impact of subtle niche differences on the evolution of CRISPR defenses. We further demonstrate potential applications of CRISPRs to the tracing of rare species and the virus exposure of individuals. This work indicates the importance of effective identification and characterization of CRISPR loci to the study of the dynamic ecology of microbiomes.},
}

Archaea/genetics
Bacteria/genetics/virology
Bacteriophages/genetics
Base Sequence
DNA, Intergenic/*genetics
*Evolution, Molecular
Genome, Bacterial
Humans
Inverted Repeat Sequences/*genetics
Metagenome/*genetics
Metagenomics
Molecular Sequence Data
Plasmids/genetics
Sequence Analysis, DNA
Streptococcus/genetics/virology

@article {pmid22719821,
year = {2012},
author = {Goll, J and Thiagarajan, M and Abubucker, S and Huttenhower, C and Yooseph, S and Methé, BA},
title = {A case study for large-scale human microbiome analysis using JCVI's metagenomics reports (METAREP).},
journal = {PloS one},
volume = {7},
number = {6},
pages = {e29044},
pmid = {22719821},
issn = {1932-6203},
support = {U54 AI084844/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; N01 AI 30071/AI/NIAID NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; N01 AI030071/AI/NIAID NIH HHS/United States ; U54-AI084844/AI/NIAID NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; },
mesh = {Bacteria/*classification/genetics ; Cluster Analysis ; Humans ; *Metagenomics ; National Institutes of Health (U.S.) ; United States ; },
abstract = {As metagenomic studies continue to increase in their number, sequence volume and complexity, the scalability of biological analysis frameworks has become a rate-limiting factor to meaningful data interpretation. To address this issue, we have developed JCVI Metagenomics Reports (METAREP) as an open source tool to query, browse, and compare extremely large volumes of metagenomic annotations. Here we present improvements to this software including the implementation of a dynamic weighting of taxonomic and functional annotation, support for distributed searches, advanced clustering routines, and integration of additional annotation input formats. The utility of these improvements to data interpretation are demonstrated through the application of multiple comparative analysis strategies to shotgun metagenomic data produced by the National Institutes of Health Roadmap for Biomedical Research Human Microbiome Project (HMP) (http://nihroadmap.nih.gov). Specifically, the scalability of the dynamic weighting feature is evaluated and established by its application to the analysis of over 400 million weighted gene annotations derived from 14 billion short reads as predicted by the HMP Unified Metabolic Analysis Network (HUMAnN) pipeline. Further, the capacity of METAREP to facilitate the identification and simultaneous comparison of taxonomic and functional annotations including biological pathway and individual enzyme abundances from hundreds of community samples is demonstrated by providing scenarios that describe how these data can be mined to answer biological questions related to the human microbiome. These strategies provide users with a reference of how to conduct similar large-scale metagenomic analyses using METAREP with their own sequence data, while in this study they reveal insights into the nature and extent of variation in taxonomic and functional profiles across body habitats and individuals. Over one thousand HMP WGS datasets and the latest open source code are available at http://www.jcvi.org/hmp-metarep.},
}

Bacteria/*classification/genetics
Cluster Analysis
Humans
*Metagenomics
National Institutes of Health (U.S.)
United States

@article {pmid22719823,
year = {2012},
author = {Li, K and Bihan, M and Yooseph, S and Methé, BA},
title = {Analyses of the microbial diversity across the human microbiome.},
journal = {PloS one},
volume = {7},
number = {6},
pages = {e32118},
pmid = {22719823},
issn = {1932-6203},
support = {U54 AI084844/AI/NIAID NIH HHS/United States ; #AI084844/AI/NIAID NIH HHS/United States ; },
mesh = {Biodiversity ; Humans ; *Metagenome ; },
abstract = {Analysis of human body microbial diversity is fundamental to understanding community structure, biology and ecology. The National Institutes of Health Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine microbial diversity within and across body habitats and individuals through pyrosequencing-based profiling of 16 S rRNA gene sequences (16 S) from habits of the oral, skin, distal gut, and vaginal body regions from over 200 healthy individuals enabling the application of statistical techniques. In this study, two approaches were applied to elucidate the nature and extent of human microbiome diversity. First, bootstrap and parametric curve fitting techniques were evaluated to estimate the maximum number of unique taxa, S(max), and taxa discovery rate for habitats across individuals. Next, our results demonstrated that the variation of diversity within low abundant taxa across habitats and individuals was not sufficiently quantified with standard ecological diversity indices. This impact from low abundant taxa motivated us to introduce a novel rank-based diversity measure, the Tail statistic, ("τ"), based on the standard deviation of the rank abundance curve if made symmetric by reflection around the most abundant taxon. Due to τ's greater sensitivity to low abundant taxa, its application to diversity estimation of taxonomic units using taxonomic dependent and independent methods revealed a greater range of values recovered between individuals versus body habitats, and different patterns of diversity within habitats. The greatest range of τ values within and across individuals was found in stool, which also exhibited the most undiscovered taxa. Oral and skin habitats revealed variable diversity patterns, while vaginal habitats were consistently the least diverse. Collectively, these results demonstrate the importance, and motivate the introduction, of several visualization and analysis methods tuned specifically for next-generation sequence data, further revealing that low abundant taxa serve as an important reservoir of genetic diversity in the human microbiome.},
}

Biodiversity
Humans
*Metagenome

@article {pmid22719824,
year = {2012},
author = {Huse, SM and Ye, Y and Zhou, Y and Fodor, AA},
title = {A core human microbiome as viewed through 16S rRNA sequence clusters.},
journal = {PloS one},
volume = {7},
number = {6},
pages = {e34242},
pmid = {22719824},
issn = {1932-6203},
support = {NIH-NHGRI U54HG004968//PHS HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; UH2 DK083993/DK/NIDDK NIH HHS/United States ; 1UH2DK083993-01/DK/NIDDK NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; NIH 1R01HG004908/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Metagenome ; RNA, Ribosomal, 16S/*genetics ; Reference Values ; },
abstract = {We explore the microbiota of 18 body sites in over 200 individuals using sequences amplified V1-V3 and the V3-V5 small subunit ribosomal RNA (16S) hypervariable regions as part of the NIH Common Fund Human Microbiome Project. The body sites with the greatest number of core OTUs, defined as OTUs shared amongst 95% or more of the individuals, were the oral sites (saliva, tongue, cheek, gums, and throat) followed by the nose, stool, and skin, while the vaginal sites had the fewest number of OTUs shared across subjects. We found that commonalities between samples based on taxonomy could sometimes belie variability at the sub-genus OTU level. This was particularly apparent in the mouth where a given genus can be present in many different oral sites, but the sub-genus OTUs show very distinct site selection, and in the vaginal sites, which are consistently dominated by the Lactobacillus genus but have distinctly different sub-genus V1-V3 OTU populations across subjects. Different body sites show approximately a ten-fold difference in estimated microbial richness, with stool samples having the highest estimated richness, followed by the mouth, throat and gums, then by the skin, nasal and vaginal sites. Richness as measured by the V1-V3 primers was consistently higher than richness measured by V3-V5. We also show that when such a large cohort is analyzed at the genus level, most subjects fit the stool "enterotype" profile, but other subjects are intermediate, blurring the distinction between the enterotypes. When analyzed at the finer-scale, OTU level, there was little or no segregation into stool enterotypes, but in the vagina distinct biotypes were apparent. Finally, we note that even OTUs present in nearly every subject, or that dominate in some samples, showed orders of magnitude variation in relative abundance emphasizing the highly variable nature across individuals.},
}

Humans
*Metagenome
RNA, Ribosomal, 16S/*genetics
Reference Values

@article {pmid22719826,
year = {2012},
author = {Wylie, KM and Truty, RM and Sharpton, TJ and Mihindukulasuriya, KA and Zhou, Y and Gao, H and Sodergren, E and Weinstock, GM and Pollard, KS},
title = {Novel bacterial taxa in the human microbiome.},
journal = {PloS one},
volume = {7},
number = {6},
pages = {e35294},
pmid = {22719826},
issn = {1932-6203},
support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; },
mesh = {DNA, Ribosomal/genetics ; Humans ; *Metagenome ; Metagenomics ; },
abstract = {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.},
}

DNA, Ribosomal/genetics
Humans
*Metagenome
Metagenomics

@article {pmid22719831,
year = {2012},
author = {Martin, J and Sykes, S and Young, S and Kota, K and Sanka, R and Sheth, N and Orvis, J and Sodergren, E and Wang, Z and Weinstock, GM and Mitreva, M},
title = {Optimizing read mapping to reference genomes to determine composition and species prevalence in microbial communities.},
journal = {PloS one},
volume = {7},
number = {6},
pages = {e36427},
pmid = {22719831},
issn = {1932-6203},
support = {U54HG004969/HG/NHGRI NIH HHS/United States ; NIH-NHGRI U54HG003079//PHS HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; NIH-NIAID UH3AI083263//PHS HHS/United States ; },
mesh = {Biodiversity ; Databases, Factual ; Humans ; *Metagenome ; *Metagenomics ; Phylogeny ; },
abstract = {The Human Microbiome Project (HMP) aims to characterize the microbial communities of 18 body sites from healthy individuals. To accomplish this, the HMP generated two types of shotgun data: reference shotgun sequences isolated from different anatomical sites on the human body and shotgun metagenomic sequences from the microbial communities of each site. The alignment strategy for characterizing these metagenomic communities using available reference sequence is important to the success of HMP data analysis. Six next-generation aligners were used to align a community of known composition against a database comprising reference organisms known to be present in that community. All aligners report nearly complete genome coverage (>97%) for strains with over 6X depth of coverage, however they differ in speed, memory requirement and ease of use issues such as database size limitations and supported mapping strategies. The selected aligner was tested across a range of parameters to maximize sensitivity while maintaining a low false positive rate. We found that constraining alignment length had more impact on sensitivity than does constraining similarity in all cases tested. However, when reference species were replaced with phylogenetic neighbors, similarity begins to play a larger role in detection. We also show that choosing the top hit randomly when multiple, equally strong mappings are available increases overall sensitivity at the expense of taxonomic resolution. The results of this study identified a strategy that was used to map over 3 tera-bases of microbial sequence against a database of more than 5,000 reference genomes in just over a month.},
}

Biodiversity
Databases, Factual
Humans
*Metagenome
*Metagenomics
Phylogeny

@article {pmid22719832,
year = {2012},
author = {Aagaard, K and Riehle, K and Ma, J and Segata, N and Mistretta, TA and Coarfa, C and Raza, S and Rosenbaum, S and Van den Veyver, I and Milosavljevic, A and Gevers, D and Huttenhower, C and Petrosino, J and Versalovic, J},
title = {A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy.},
journal = {PloS one},
volume = {7},
number = {6},
pages = {e36466},
pmid = {22719832},
issn = {1932-6203},
support = {DP2120OD001500-01/OD/NIH HHS/United States ; #R01DK080558-01/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; NIHU54HG004969/HG/NHGRI NIH HHS/United States ; R01 DK080558/DK/NIDDK NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; UH3 DK083990L/DK/NIDDK NIH HHS/United States ; NIH 1R01HG005969/HG/NHGRI NIH HHS/United States ; },
mesh = {Adult ; Bacteria/classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Female ; Humans ; *Metagenome ; *Metagenomics ; Pregnancy ; Vagina/*microbiology ; },
abstract = {While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age.},
}

Adult
Bacteria/classification/genetics/isolation & purification
DNA, Bacterial/genetics
Female
Humans
*Metagenome
*Metagenomics
Pregnancy
Vagina/*microbiology

@article {pmid22720093,
year = {2012},
author = {, },
title = {Evaluation of 16S rDNA-based community profiling for human microbiome research.},
journal = {PloS one},
volume = {7},
number = {6},
pages = {e39315},
pmid = {22720093},
issn = {1932-6203},
support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; HHSN272200900008C/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; HHSN2722009000018C//PHS HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; HHSN272200900001C/AI/NIAID NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; 1U01HG004866/HG/NHGRI NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; },
mesh = {Bacteria/classification/genetics ; Bayes Theorem ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/*genetics ; },
abstract = {The Human Microbiome Project will establish a reference data set for analysis of the microbiome of healthy adults by surveying multiple body sites from 300 people and generating data from over 12,000 samples. To characterize these samples, the participating sequencing centers evaluated and adopted 16S rDNA community profiling protocols for ABI 3730 and 454 FLX Titanium sequencing. In the course of establishing protocols, we examined the performance and error characteristics of each technology, and the relationship of sequence error to the utility of 16S rDNA regions for classification- and OTU-based analysis of community structure. The data production protocols used for this work are those used by the participating centers to produce 16S rDNA sequence for the Human Microbiome Project. Thus, these results can be informative for interpreting the large body of clinical 16S rDNA data produced for this project.},
}

Bacteria/classification/genetics
Bayes Theorem
Humans
*Metagenome
RNA, Ribosomal, 16S/*genetics

@article {pmid22792232,
year = {2012},
author = {Markowitz, VM and Chen, IM and Chu, K and Szeto, E and Palaniappan, K and Jacob, B and Ratner, A and Liolios, K and Pagani, I and Huntemann, M and Mavromatis, K and Ivanova, NN and Kyrpides, NC},
title = {IMG/M-HMP: a metagenome comparative analysis system for the Human Microbiome Project.},
journal = {PloS one},
volume = {7},
number = {7},
pages = {e40151},
pmid = {22792232},
issn = {1932-6203},
support = {U01 HG004866/HG/NHGRI NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; },
mesh = {Archaea/genetics ; Bacteria/genetics ; *Database Management Systems ; *Databases, Genetic ; Eukaryota/genetics ; Humans ; *Internet ; Metagenome/*genetics ; User-Computer Interface ; },
abstract = {The Integrated Microbial Genomes and Metagenomes (IMG/M) resource is a data management system that supports the analysis of sequence data from microbial communities in the integrated context of all publicly available draft and complete genomes from the three domains of life as well as a large number of plasmids and viruses. IMG/M currently contains thousands of genomes and metagenome samples with billions of genes. IMG/M-HMP is an IMG/M data mart serving the US National Institutes of Health (NIH) Human Microbiome Project (HMP), focussed on HMP generated metagenome datasets, and is one of the central resources provided from the HMP Data Analysis and Coordination Center (DACC). IMG/M-HMP is available at http://www.hmpdacc-resources.org/imgm_hmp/.},
}

Archaea/genetics
Bacteria/genetics
*Database Management Systems
*Databases, Genetic
Eukaryota/genetics
Humans
*Internet
Metagenome/*genetics
User-Computer Interface

@article {pmid22807668,
year = {2012},
author = {Faust, K and Sathirapongsasuti, JF and Izard, J and Segata, N and Gevers, D and Raes, J and Huttenhower, C},
title = {Microbial co-occurrence relationships in the human microbiome.},
journal = {PLoS computational biology},
volume = {8},
number = {7},
pages = {e1002606},
pmid = {22807668},
issn = {1553-7358},
support = {U54HG004969/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; },
mesh = {Bacteria/*classification ; *Bacterial Physiological Phenomena ; Computational Biology ; DNA, Bacterial/chemistry ; Ecosystem ; Female ; Gastrointestinal Tract/microbiology ; Genes, rRNA/genetics ; Humans ; Linear Models ; Male ; Metagenome/*physiology ; Microbial Interactions/physiology ; Nasal Cavity/microbiology ; Phylogeny ; Skin/microbiology ; Vagina/microbiology ; },
abstract = {The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles of this cohort, resulting in a global network of 3,005 significant co-occurrence and co-exclusion relationships between 197 clades occurring throughout the human microbiome. This network revealed strong niche specialization, with most microbial associations occurring within body sites and a number of accompanying inter-body site relationships. Microbial communities within the oropharynx grouped into three distinct habitats, which themselves showed no direct influence on the composition of the gut microbiota. Conversely, niches such as the vagina demonstrated little to no decomposition into region-specific interactions. Diverse mechanisms underlay individual interactions, with some such as the co-exclusion of Porphyromonaceae family members and Streptococcus in the subgingival plaque supported by known biochemical dependencies. These differences varied among broad phylogenetic groups as well, with the Bacilli and Fusobacteria, for example, both enriched for exclusion of taxa from other clades. Comparing phylogenetic versus functional similarities among bacteria, we show that dominant commensal taxa (such as Prevotellaceae and Bacteroides in the gut) often compete, while potential pathogens (e.g. Treponema and Prevotella in the dental plaque) are more likely to co-occur in complementary niches. This approach thus serves to open new opportunities for future targeted mechanistic studies of the microbial ecology of the human microbiome.},
}

Bacteria/*classification
*Bacterial Physiological Phenomena
Computational Biology
DNA, Bacterial/chemistry
Ecosystem
Female
Gastrointestinal Tract/microbiology
Genes, rRNA/genetics
Humans
Linear Models
Male
Metagenome/*physiology
Microbial Interactions/physiology
Nasal Cavity/microbiology
Phylogeny
Skin/microbiology
Vagina/microbiology

@article {pmid22841660,
year = {2012},
author = {Liu, L and Chen, X and Skogerbø, G and Zhang, P and Chen, R and He, S and Huang, DW},
title = {The human microbiome: a hot spot of microbial horizontal gene transfer.},
journal = {Genomics},
volume = {100},
number = {5},
pages = {265-270},
doi = {10.1016/j.ygeno.2012.07.012},
pmid = {22841660},
issn = {1089-8646},
mesh = {*Biota ; Computational Biology ; Gene Transfer, Horizontal/*genetics ; Genes, Bacterial/*genetics ; Genomics/*methods ; Humans ; Metagenome/*genetics ; Molecular Sequence Annotation ; },
abstract = {The human body harbors numerous microbes, and here exists a close relationship between microbes and human health. The Human Microbiome Project has generated whole genome sequences of several hundred human microbes. In this study, we identified horizontal gene transfer (HGT) events in human microbes and tried to elucidate the relationships between the gene-transferring microbes. A total of 13,514 high confidence HGT genes were identified in 308 human microbes. The horizontally transferred genes were enriched for Gene Ontology terms pertaining to catalytic functions and metabolic processes. Construction of an HGT event network suggested that the human microbes could be divided into specific communities which only partly overlap their distribution in human body. Our research suggests that human microbiome may facilitate frequent horizontal gene transfer among bacteria in human body. Awareness of HGT in human microbiome may aid our understanding of the relationship between the human microbiome and human health.},
}

*Biota
Computational Biology
Gene Transfer, Horizontal/*genetics
Genes, Bacterial/*genetics
Genomics/*methods
Humans
Metagenome/*genetics
Molecular Sequence Annotation

@article {pmid22848458,
year = {2012},
author = {Fodor, AA and DeSantis, TZ and Wylie, KM and Badger, JH and Ye, Y and Hepburn, T and Hu, P and Sodergren, E and Liolios, K and Huot-Creasy, H and Birren, BW and Earl, AM},
title = {The "most wanted" taxa from the human microbiome for whole genome sequencing.},
journal = {PloS one},
volume = {7},
number = {7},
pages = {e41294},
pmid = {22848458},
issn = {1932-6203},
support = {U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; HHSN272200900008C/AI/NIAID NIH HHS/United States ; HHSN272200900001C/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; HHSN2722009000018C//PHS HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; },
mesh = {Bacteria/*classification/*genetics ; Cohort Studies ; Female ; *Genes, Bacterial ; Genes, rRNA/*genetics ; Humans ; Male ; Metagenome/*genetics ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; },
abstract = {The goal of the Human Microbiome Project (HMP) is to generate a comprehensive catalog of human-associated microorganisms including reference genomes representing the most common species. Toward this goal, the HMP has characterized the microbial communities at 18 body habitats in a cohort of over 200 healthy volunteers using 16S rRNA gene (16S) sequencing and has generated nearly 1,000 reference genomes from human-associated microorganisms. To determine how well current reference genome collections capture the diversity observed among the healthy microbiome and to guide isolation and future sequencing of microbiome members, we compared the HMP's 16S data sets to several reference 16S collections to create a 'most wanted' list of taxa for sequencing. Our analysis revealed that the diversity of commonly occurring taxa within the HMP cohort microbiome is relatively modest, few novel taxa are represented by these OTUs and many common taxa among HMP volunteers recur across different populations of healthy humans. Taken together, these results suggest that it should be possible to perform whole-genome sequencing on a large fraction of the human microbiome, including the 'most wanted', and that these sequences should serve to support microbiome studies across multiple cohorts. Also, in stark contrast to other taxa, the 'most wanted' organisms are poorly represented among culture collections suggesting that novel culture- and single-cell-based methods will be required to isolate these organisms for sequencing.},
}

Bacteria/*classification/*genetics
Cohort Studies
Female
*Genes, Bacterial
Genes, rRNA/*genetics
Humans
Male
Metagenome/*genetics
RNA, Bacterial/genetics
RNA, Ribosomal, 16S/genetics
Sequence Analysis, DNA/*methods

@article {pmid22850139,
year = {2012},
author = {McGuire, AL and Achenbaum, LS and Whitney, SN and Slashinski, MJ and Versalovic, J and Keitel, WA and McCurdy, SA},
title = {Perspectives on human microbiome research ethics.},
journal = {Journal of empirical research on human research ethics : JERHRE},
volume = {7},
number = {3},
pages = {1-14},
pmid = {22850139},
issn = {1556-2654},
support = {R01 HG004853/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; },
mesh = {Adult ; Aged ; *Ethics, Research ; Female ; Humans ; Information Dissemination ; Informed Consent ; Interviews as Topic ; Male ; *Metagenome ; Metagenomics/*ethics/legislation & jurisprudence ; Middle Aged ; National Institutes of Health (U.S.) ; Research Personnel ; Research Subjects ; United States ; },
abstract = {Study of ethical, legal, and social implications (ELSI) of human microbiome research has been integral to the Human Microbiome Project (HMP). This study explores core ELSI issues that arose during the first phase of the HMP from the perspective of individuals involved in the research. We conducted semi-structured in-depth interviews with investigators and NIH employees ("investigators") involved in the HMP, and with individuals recruited to participate in the HMP Healthy Cohort Study at Baylor College of Medicine ("recruits"). We report findings related to three major ELSI issues: informed consent, data sharing, and return of results. Our findings demonstrate that investigators and recruits were similarly sensitive to these issues yet generally comfortable with study design in light of current knowledge about the microbiome.},
}

Adult
Aged
*Ethics, Research
Female
Humans
Information Dissemination
Informed Consent
Interviews as Topic
Male
*Metagenome
Metagenomics/*ethics/legislation & jurisprudence
Middle Aged
National Institutes of Health (U.S.)
Research Personnel
Research Subjects
United States

@article {pmid22902418,
year = {2012},
author = {Triggle, DJ},
title = {Nous sommes tous des bacteries: implications for medicine, pharmacology and public health.},
journal = {Biochemical pharmacology},
volume = {84},
number = {12},
pages = {1543-1550},
doi = {10.1016/j.bcp.2012.08.005},
pmid = {22902418},
issn = {1873-2968},
mesh = {*Bacteria ; Humans ; *Metagenome ; *Pharmacology ; *Public Health ; },
abstract = {As a species we humans are outnumbered by bacteria in both cell and gene count. This somewhat humbling observation is key to the increasing recognition that the long-standing symbiotic and commensal relations between Homo sapiens and bacteria are of great significance to basic human physiology and health. Knowledge of our human bacterial environment is contributing to an understanding of a variety of disorders including obesity and metabolic syndrome, cardiovascular disease, immunity, and neuronal development and behavior. The Human Microbiome Project is providing a genetic and ecological analysis and will serve as a parallel to the Human Genome Project. Exploration of the chemical space utilized by bacteria will contribute to the development of new small molecule therapeutic agents, including new antibiotics. And genetically re-engineered bacteria are proving to be of potential value as actual therapeutic entities. Our understanding of our bacterial world has the capability to transform radically our current approach to human health diverting it from an emphasis on acute treatments to living in healthy harmony with both our internal and external environments.},
}

*Bacteria
Humans
*Metagenome
*Pharmacology
*Public Health

@article {pmid22904687,
year = {2012},
author = {Gevers, D and Knight, R and Petrosino, JF and Huang, K and McGuire, AL and Birren, BW and Nelson, KE and White, O and Methé, BA and Huttenhower, C},
title = {The Human Microbiome Project: a community resource for the healthy human microbiome.},
journal = {PLoS biology},
volume = {10},
number = {8},
pages = {e1001377},
pmid = {22904687},
issn = {1545-7885},
support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; },
mesh = {Computational Biology ; Ecosystem ; Genes, rRNA ; *Genomics ; Health ; High-Throughput Nucleotide Sequencing ; Humans ; *Internet ; *Metagenome ; Organizations/*organization & administration ; Phylogeny ; RNA, Ribosomal, 16S/analysis/genetics ; },
abstract = {This manuscript describes the NIH Human Microbiome Project, including a brief review of human microbiome research, a history of the project, and a comprehensive overview of the consortium's recent collection of publications analyzing the human microbiome.},
}

Computational Biology
Ecosystem
Genes, rRNA
*Genomics
Health
High-Throughput Nucleotide Sequencing
Humans
*Internet
*Metagenome
Organizations/*organization & administration
Phylogeny
RNA, Ribosomal, 16S/analysis/genetics

@article {pmid23015504,
year = {2012},
author = {Rogers, AB},
title = {Gastric Helicobacter spp. in animal models: pathogenesis and modulation by extragastric coinfections.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {921},
number = {},
pages = {175-188},
doi = {10.1007/978-1-62703-005-2_21},
pmid = {23015504},
issn = {1940-6029},
mesh = {Animals ; *Coinfection ; *Disease Models, Animal ; Helicobacter/*pathogenicity ; Helicobacter Infections/*complications/*microbiology ; Humans ; Stomach/*microbiology ; },
abstract = {Animal models are used to study complex host, microbial, and environmental influences associated with gastric Helicobacter infection. Evidence that gastric helicobacters are pathogenic in animals first came from ferrets. Felids, nonhuman primates, and many other species also harbor stomach helicobacters. Today, mice are preferred by most researchers for scientific investigation because of cost-efficiencies, rapid reproduction, choice of laboratory reagents, and availability of genetically engineered models. Infection with Helicobacter felis or H. pylori Sydney strain-1 in appropriate mouse strains produces disease with remarkable similarities to H. pylori in humans. Due to recent advances in genetic engineering, in vivo imaging, and system-wide genomics and proteomics, these models will become even more widespread in the future. Recently, it has been shown that extragastric infections can dramatically affect the severity of disease induced by gastric Helicobacter spp. through heterologous immunity. These models provide proof-of-principle for the "African enigma" wherein gastric cancer is underrepresented in low-lying tropical countries with concurrently high H. pylori and internal parasite prevalence. Helicobacter gastritis and carcinogenesis in mouse models may be augmented or ameliorated by other infectious agents depending on the character of the invoked immune response. Knowledge gained from the Human Microbiome Project and other investigations is certain to shed new light on the influence of extragastric bacterial, viral, fungal, and parasitic coinfections on H. pylori-associated peptic ulcer disease and gastric adenocarcinoma.},
}

Animals
*Coinfection
*Disease Models, Animal
Helicobacter/*pathogenicity
Helicobacter Infections/*complications/*microbiology
Humans
Stomach/*microbiology

@article {pmid23028285,
year = {2012},
author = {Friedman, J and Alm, EJ},
title = {Inferring correlation networks from genomic survey data.},
journal = {PLoS computational biology},
volume = {8},
number = {9},
pages = {e1002687},
pmid = {23028285},
issn = {1553-7358},
mesh = {Chromosome Mapping/*methods ; Computer Simulation ; *Genetics, Population ; Genome, Bacterial/*genetics ; Humans ; Microbial Consortia/*genetics ; *Models, Genetic ; Recombination, Genetic/*genetics ; Statistics as Topic ; },
abstract = {High-throughput sequencing based techniques, such as 16S rRNA gene profiling, have the potential to elucidate the complex inner workings of natural microbial communities - be they from the world's oceans or the human gut. A key step in exploring such data is the identification of dependencies between members of these communities, which is commonly achieved by correlation analysis. However, it has been known since the days of Karl Pearson that the analysis of the type of data generated by such techniques (referred to as compositional data) can produce unreliable results since the observed data take the form of relative fractions of genes or species, rather than their absolute abundances. Using simulated and real data from the Human Microbiome Project, we show that such compositional effects can be widespread and severe: in some real data sets many of the correlations among taxa can be artifactual, and true correlations may even appear with opposite sign. Additionally, we show that community diversity is the key factor that modulates the acuteness of such compositional effects, and develop a new approach, called SparCC (available at https://bitbucket.org/yonatanf/sparcc), which is capable of estimating correlation values from compositional data. To illustrate a potential application of SparCC, we infer a rich ecological network connecting hundreds of interacting species across 18 sites on the human body. Using the SparCC network as a reference, we estimated that the standard approach yields 3 spurious species-species interactions for each true interaction and misses 60% of the true interactions in the human microbiome data, and, as predicted, most of the erroneous links are found in the samples with the lowest diversity.},
}

Chromosome Mapping/*methods
Computer Simulation
*Genetics, Population
Genome, Bacterial/*genetics
Humans
Microbial Consortia/*genetics
*Models, Genetic
Recombination, Genetic/*genetics
Statistics as Topic

@article {pmid23071716,
year = {2012},
author = {Conlan, S and Kong, HH and Segre, JA},
title = {Species-level analysis of DNA sequence data from the NIH Human Microbiome Project.},
journal = {PloS one},
volume = {7},
number = {10},
pages = {e47075},
pmid = {23071716},
issn = {1932-6203},
support = {UH3-AR057504/AR/NIAMS NIH HHS/United States ; //Intramural NIH HHS/United States ; },
mesh = {Databases, Nucleic Acid ; Drug Resistance, Bacterial ; Enterococcus faecalis/classification/*genetics ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Klebsiella pneumoniae/classification/*genetics ; *Metagenome ; Mouth/microbiology ; National Institutes of Health (U.S.) ; Phylogeny ; *RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; Skin/microbiology ; Staphylococcus aureus/classification/*genetics ; United States ; Vagina/microbiology ; },
abstract = {BACKGROUND: Outbreaks of antibiotic-resistant bacterial infections emphasize the importance of surveillance of potentially pathogenic bacteria. Genomic sequencing of clinical microbiological specimens expands our capacity to study cultivable, fastidious and uncultivable members of the bacterial community. Herein, we compared the primary data collected by the NIH's Human Microbiome Project (HMP) with published epidemiological surveillance data of Staphylococcus aureus.

METHODS: The HMP's initial dataset contained microbial survey data from five body regions (skin, nares, oral cavity, gut and vagina) of 242 healthy volunteers. A significant component of the HMP dataset was deep sequencing of the 16S ribosomal RNA gene, which contains variable regions enabling taxonomic classification. Since species-level identification is essential in clinical microbiology, we built a reference database and used phylogenetic placement followed by most recent common ancestor classification to look at the species distribution for Staphylococcus, Klebsiella and Enterococcus.

MAIN RESULTS: We show that selecting the accurate region of the 16S rRNA gene to sequence is analogous to carefully selecting culture conditions to distinguish closely related bacterial species. Analysis of the HMP data showed that Staphylococcus aureus was present in the nares of 36% of healthy volunteers, consistent with culture-based epidemiological data. Klebsiella pneumoniae and Enterococcus faecalis were found less frequently, but across many habitats.

CONCLUSIONS: This work demonstrates that large 16S rRNA survey studies can be used to support epidemiological goals in the context of an increasing awareness that microbes flourish and compete within a larger bacterial community. This study demonstrates how genomic techniques and information could be critically important to trace microbial evolution and implement hospital infection control.},
}

Databases, Nucleic Acid
Drug Resistance, Bacterial
Enterococcus faecalis/classification/*genetics
Female
Gastrointestinal Tract/microbiology
Humans
Klebsiella pneumoniae/classification/*genetics
*Metagenome
Mouth/microbiology
National Institutes of Health (U.S.)
Phylogeny
*RNA, Ribosomal, 16S
Sequence Analysis, DNA
Skin/microbiology
Staphylococcus aureus/classification/*genetics
United States
Vagina/microbiology

@article {pmid23131830,
year = {2012},
author = {Rogers, GB and Bruce, KD},
title = {Exploring the parallel development of microbial systems in neonates with cystic fibrosis.},
journal = {mBio},
volume = {3},
number = {6},
pages = {e00408-12},
pmid = {23131830},
issn = {2150-7511},
mesh = {*Biota ; Cystic Fibrosis/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Respiratory System/*microbiology ; },
abstract = {Recent studies have greatly extended our understanding of the microbiota present in and on the human body. Here, advanced sequencing strategies have provided unprecedented analytical power. The important implications that the emerging data have for human health emphasize the need to intensify research in this area (D. A. Relman, Nature 486:194-195, 2012). It is already clear from these studies that the microbiotas characterized in different body locations of healthy individuals are both complex and diverse (The Human Microbiome Project Consortium, Nature 486:215-221). These studies also provide a point of contrast for investigations that aim to characterize the microbiota present in disease conditions. In this regard, Madan et al. (mBio 3(4):e00251-12, 2012) monitored the development over time of microbiota in the oropharynges and feces of neonates with cystic fibrosis and explored the potential for interactions between these complex microbial systems.},
}

*Biota
Cystic Fibrosis/*microbiology
Gastrointestinal Tract/*microbiology
Humans
*Metagenome
Respiratory System/*microbiology

@article {pmid23140990,
year = {2013},
author = {Morgan, XC and Segata, N and Huttenhower, C},
title = {Biodiversity and functional genomics in the human microbiome.},
journal = {Trends in genetics : TIG},
volume = {29},
number = {1},
pages = {51-58},
pmid = {23140990},
issn = {0168-9525},
support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; 1R01HG005969-01/HG/NHGRI NIH HHS/United States ; },
mesh = {*Biodiversity ; Computational Biology ; Gastrointestinal Tract/metabolism/*microbiology ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics/physiology ; Phylogeny ; },
abstract = {Over the course of our lives, humans are colonized by a tremendous diversity of commensal microbes, which comprise the human microbiome. The collective genetic potential (metagenome) of the human microbiome is orders of magnitude more than the human genome, and it profoundly affects human health and disease in ways we are only beginning to understand. Advances in computing and high-throughput sequencing have enabled population-level surveys such as MetaHIT and the recently released Human Microbiome Project, detailed investigations of the microbiome in human disease, and mechanistic studies employing gnotobiotic model organisms. The resulting knowledge of human microbiome composition, function, and range of variation across multiple body sites has begun to assemble a rich picture of commensal host-microbe and microbe-microbe interactions as well as their roles in human health and disease and their potential as diagnostic and therapeutic tools.},
}

*Biodiversity
Computational Biology
Gastrointestinal Tract/metabolism/*microbiology
Genomics/*methods
High-Throughput Nucleotide Sequencing
Humans
Microbiota/*genetics/physiology
Phylogeny

@article {pmid23141757,
year = {2013},
author = {Peyyala, R and Ebersole, JL},
title = {Multispecies biofilms and host responses: "discriminating the trees from the forest".},
journal = {Cytokine},
volume = {61},
number = {1},
pages = {15-25},
pmid = {23141757},
issn = {1096-0023},
support = {P20 GM103538/GM/NIGMS NIH HHS/United States ; R21 DE018177/DE/NIDCR NIH HHS/United States ; DE 018177/DE/NIDCR NIH HHS/United States ; },
mesh = {Biodiversity ; *Biofilms ; Host-Pathogen Interactions/*immunology/physiology ; Humans ; Metagenome/immunology ; Mouth/*microbiology/*pathology ; Periodontal Diseases/*microbiology ; },
abstract = {Periodontal diseases reflect a tissue destructive process of the hard and soft tissues of the periodontium that are initiated by the accumulation of multispecies bacterial biofilms in the subgingival sulcus. This accumulation, in both quantity and quality of bacteria, results in a chronic immunoinflammatory response of the host to control this noxious challenge, leading to collateral damage of the tissues. As knowledge of the characteristics of the host-bacterial interactions in the oral cavity has expanded, new knowledge has become available on the complexity of the microbial challenge and the repertoire of host responses to this challenge. Recent results from the Human Microbiome Project continue to extend the array of taxa, genera, and species of bacteria that inhabit the multiple niches in the oral cavity; however, there is rather sparse information regarding variations in how host cells discriminate commensal from pathogenic species, as well as how the host response is affected by the three-dimensional architecture and interbacterial interactions that occur in the oral biofilms. This review provides some insights into these processes by including existing literature on the biology of nonoral bacterial biofilms, and the more recent literature just beginning to document how the oral cavity responds to multispecies biofilms.},
}

Biodiversity
*Biofilms
Host-Pathogen Interactions/*immunology/physiology
Humans
Metagenome/immunology
Mouth/*microbiology/*pathology
Periodontal Diseases/*microbiology

@article {pmid23165986,
year = {2013},
author = {Aagaard, K and Petrosino, J and Keitel, W and Watson, M and Katancik, J and Garcia, N and Patel, S and Cutting, M and Madden, T and Hamilton, H and Harris, E and Gevers, D and Simone, G and McInnes, P and Versalovic, J},
title = {The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {27},
number = {3},
pages = {1012-1022},
pmid = {23165986},
issn = {1530-6860},
support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; K23 HD070979/HD/NICHD NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Body Mass Index ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; *Metagenome ; Mouth/*microbiology ; Skin/*microbiology ; Specimen Handling/*methods ; Vagina/*microbiology ; },
abstract = {The Human Microbiome Project used rigorous good clinical practice standards to complete comprehensive body site sampling in healthy 18- to 40-yr-old adults, creating an unparalleled reference set of microbiome specimens. To ensure that specimens represented minimally perturbed microbiomes, we first screened potential participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 yr, mean BMI 24 kg/m, 20.0% racial minority, and 10.7% Hispanic). We obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3 times (mean 72 d after the second sampling; range 30-224 d). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to 4 centers for metagenomic sequencing. Our clinical design and well-defined reference cohort has laid a foundation for microbiome research.},
}

Adolescent
Adult
Body Mass Index
Female
Gastrointestinal Tract/*microbiology
Humans
Male
*Metagenome
Mouth/*microbiology
Skin/*microbiology
Specimen Handling/*methods
Vagina/*microbiology

@article {pmid23194438,
year = {2012},
author = {Saad, R and Rizkallah, MR and Aziz, RK},
title = {Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes.},
journal = {Gut pathogens},
volume = {4},
number = {1},
pages = {16},
pmid = {23194438},
issn = {1757-4749},
abstract = {The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.},
}

@article {pmid23196853,
year = {2013},
author = {Buccigrossi, V and Nicastro, E and Guarino, A},
title = {Functions of intestinal microflora in children.},
journal = {Current opinion in gastroenterology},
volume = {29},
number = {1},
pages = {31-38},
doi = {10.1097/MOG.0b013e32835a3500},
pmid = {23196853},
issn = {1531-7056},
mesh = {Child ; Enterocolitis, Necrotizing/microbiology/therapy ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestinal Diseases/*microbiology/therapy ; Intestines/*microbiology ; Irritable Bowel Syndrome/microbiology/therapy ; Metagenome/*physiology ; Probiotics/therapeutic use ; },
abstract = {PURPOSE OF REVIEW: This review discusses the structural composition of intestinal microbiota, the functional relationship between the latter and the host, and the role of abnormal microflora in chronic diseases.

RECENT FINDINGS: A more complete view of the gut microbiota is being developed following the Human Microbiome Project. The microflora in children is plastic, susceptible to changes in response to diet modifications, antibiotic treatment and other events, providing the opportunity to study its functional role. Increasing evidence highlights the role of nutrition in the age-related development of microflora. Eubiosis, that is, a normal microflora structure, provides protection against infections, educates the immune system, ensures tolerance to foods, and contributes to nutrient digestion and energy harvest. Changes in microflora, consisting in the overpresence of harmful species or underpresence of commensal species, or dysbiosis produce dysfunctions, such as intestinal inflammation or dysmotility. Moreover abnormal pattern of microflora have been consistently detected in specific diseases.

SUMMARY: A relationship exists between eubiosis and functions and conversely between dysbiosis and dysfunctions or even diseases. Abnormalities in microflora composition may trigger or contribute to specific diseases. This raises the hypothesis to target microflora in order to restore eubiosis through the use of antibiotics, probiotics or nutrients.},
}

Child
Enterocolitis, Necrotizing/microbiology/therapy
Humans
Inflammatory Bowel Diseases/microbiology
Intestinal Diseases/*microbiology/therapy
Intestines/*microbiology
Irritable Bowel Syndrome/microbiology/therapy
Metagenome/*physiology
Probiotics/therapeutic use

@article {pmid23209389,
year = {2012},
author = {Gevers, D and Pop, M and Schloss, PD and Huttenhower, C},
title = {Bioinformatics for the Human Microbiome Project.},
journal = {PLoS computational biology},
volume = {8},
number = {11},
pages = {e1002779},
pmid = {23209389},
issn = {1553-7358},
support = {U54HG004969/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; },
mesh = {*Computational Biology ; Database Management Systems ; Databases, Factual ; Humans ; *Metagenome ; Metagenomics ; },
}

*Computational Biology
Database Management Systems
Databases, Factual
Humans
*Metagenome
Metagenomics

@article {pmid23216677,
year = {2012},
author = {Tyakht, AV and Popenko, AS and Belenikin, MS and Altukhov, IA and Pavlenko, AV and Kostryukova, ES and Selezneva, OV and Larin, AK and Karpova, IY and Alexeev, DG},
title = {MALINA: a web service for visual analytics of human gut microbiota whole-genome metagenomic reads.},
journal = {Source code for biology and medicine},
volume = {7},
number = {1},
pages = {13},
pmid = {23216677},
issn = {1751-0473},
abstract = {MALINA is a web service for bioinformatic analysis of whole-genome metagenomic data obtained from human gut microbiota sequencing. As input data, it accepts metagenomic reads of various sequencing technologies, including long reads (such as Sanger and 454 sequencing) and next-generation (including SOLiD and Illumina). It is the first metagenomic web service that is capable of processing SOLiD color-space reads, to authors' knowledge. The web service allows phylogenetic and functional profiling of metagenomic samples using coverage depth resulting from the alignment of the reads to the catalogue of reference sequences which are built into the pipeline and contain prevalent microbial genomes and genes of human gut microbiota. The obtained metagenomic composition vectors are processed by the statistical analysis and visualization module containing methods for clustering, dimension reduction and group comparison. Additionally, the MALINA database includes vectors of bacterial and functional composition for human gut microbiota samples from a large number of existing studies allowing their comparative analysis together with user samples, namely datasets from Russian Metagenome project, MetaHIT and Human Microbiome Project (downloaded from http://hmpdacc.org). MALINA is made freely available on the web at http://malina.metagenome.ru. The website is implemented in JavaScript (using Ext JS), Microsoft .NET Framework, MS SQL, Python, with all major browsers supported.},
}

@article {pmid23223587,
year = {2013},
author = {Mitsuma, SF and Mansour, MK and Dekker, JP and Kim, J and Rahman, MZ and Tweed-Kent, A and Schuetz, P},
title = {Promising new assays and technologies for the diagnosis and management of infectious diseases.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {56},
number = {7},
pages = {996-1002},
pmid = {23223587},
issn = {1537-6591},
support = {T32 AI007061/AI/NIAID NIH HHS/United States ; T32-AI007061-35/AI/NIAID NIH HHS/United States ; },
mesh = {Clinical Laboratory Techniques/*methods/trends ; Communicable Diseases/*diagnosis ; Humans ; },
abstract = {In the first decade of the 21st century, we have seen the completion of the human genome project and marked progress in the human microbiome project. The vast amount of data generated from these efforts combined with advances in molecular and biomedical technologies have led to the development of a multitude of assays and technologies that may be useful in the diagnosis and management of infectious diseases. Here, we identify several new assays and technologies that have recently come into clinical use or have potential for clinical use in the near future. The scope of this review is broad and includes topics such as the serum marker procalcitonin, gene expression profiling, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and nucleic acid aptamers. Principles that underlie each assay or technology, their clinical applications, and potential strengths and limitations are addressed.},
}

Clinical Laboratory Techniques/*methods/trends
Communicable Diseases/*diagnosis
Humans

@article {pmid23281612,
year = {2012},
author = {Harwich, MD and Serrano, MG and Fettweis, JM and Alves, JM and Reimers, MA and , and Buck, GA and Jefferson, KK},
title = {Genomic sequence analysis and characterization of Sneathia amnii sp. nov.},
journal = {BMC genomics},
volume = {13 Suppl 8},
number = {Suppl 8},
pages = {S4},
pmid = {23281612},
issn = {1471-2164},
support = {2P30 CA16059/CA/NCI NIH HHS/United States ; 4UH3AI083263/AI/NIAID NIH HHS/United States ; 5P30NS047463/NS/NINDS NIH HHS/United States ; },
mesh = {Anti-Bacterial Agents/pharmacology ; Female ; *Genome, Bacterial ; Humans ; Leptotrichia/classification/drug effects/*genetics ; Metagenome ; Microbial Sensitivity Tests ; Phenotype ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Sequence Analysis, DNA ; Vagina/microbiology ; Virulence/genetics ; },
abstract = {BACKGROUND: Bacteria of the genus Sneathia are emerging as potential pathogens of the female reproductive tract. Species of Sneathia, which were formerly grouped with Leptotrichia, can be part of the normal microbiota of the genitourinary tracts of men and women, but they are also associated with a variety of clinical conditions including bacterial vaginosis, preeclampsia, preterm labor, spontaneous abortion, post-partum bacteremia and other invasive infections. Sneathia species also exhibit a significant correlation with sexually transmitted diseases and cervical cancer. Because Sneathia species are fastidious and rarely cultured successfully in vitro; and the genomes of members of the genus had until now not been characterized, very little is known about the physiology or the virulence of these organisms.

RESULTS: Here, we describe a novel species, Sneathia amnii sp. nov, which closely resembles bacteria previously designated "Leptotrichia amnionii". As part of the Vaginal Human Microbiome Project at VCU, a vaginal isolate of S. amnii sp. nov. was identified, successfully cultured and bacteriologically cloned. The biochemical characteristics and virulence properties of the organism were examined in vitro, and the genome of the organism was sequenced, annotated and analyzed. The analysis revealed a reduced circular genome of ~1.34 Mbp, containing ~1,282 protein-coding genes. Metabolic reconstruction of the bacterium reflected its biochemical phenotype, and several genes potentially associated with pathogenicity were identified.

CONCLUSIONS: Bacteria with complex growth requirements frequently remain poorly characterized and, as a consequence, their roles in health and disease are unclear. Elucidation of the physiology and identification of genes putatively involved in the metabolism and virulence of S. amnii may lead to a better understanding of the role of this potential pathogen in bacterial vaginosis, preterm birth, and other issues associated with vaginal and reproductive health.},
}

Anti-Bacterial Agents/pharmacology
Female
*Genome, Bacterial
Humans
Leptotrichia/classification/drug effects/*genetics
Metagenome
Microbial Sensitivity Tests
Phenotype
Phylogeny
RNA, Ribosomal, 16S/genetics
*Sequence Analysis, DNA
Vagina/microbiology
Virulence/genetics

@article {pmid23282177,
year = {2012},
author = {Fettweis, JM and Serrano, MG and Sheth, NU and Mayer, CM and Glascock, AL and Brooks, JP and Jefferson, KK and , and Buck, GA},
title = {Species-level classification of the vaginal microbiome.},
journal = {BMC genomics},
volume = {13 Suppl 8},
number = {Suppl 8},
pages = {S17},
pmid = {23282177},
issn = {1471-2164},
support = {UH2/UH3AI083263/AI/NIAID NIH HHS/United States ; },
mesh = {Algorithms ; Bacteria/*classification/genetics ; Databases, Genetic ; Female ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; Vagina/*microbiology ; },
abstract = {BACKGROUND: The application of next-generation sequencing to the study of the vaginal microbiome is revealing the spectrum of microbial communities that inhabit the human vagina. High-resolution identification of bacterial taxa, minimally to the species level, is necessary to fully understand the association of the vaginal microbiome with bacterial vaginosis, sexually transmitted infections, pregnancy complications, menopause, and other physiological and infectious conditions. However, most current taxonomic assignment strategies based on metagenomic 16S rDNA sequence analysis provide at best a genus-level resolution. While surveys of 16S rRNA gene sequences are common in microbiome studies, few well-curated, body-site-specific reference databases of 16S rRNA gene sequences are available, and no such resource is available for vaginal microbiome studies.

RESULTS: We constructed the Vaginal 16S rDNA Reference Database, a comprehensive and non-redundant database of 16S rDNA reference sequences for bacterial taxa likely to be associated with vaginal health, and we developed STIRRUPS, a new method that employs the USEARCH algorithm with a curated reference database for rapid species-level classification of 16S rDNA partial sequences. The method was applied to two datasets of V1-V3 16S rDNA reads: one generated from a mock community containing DNA from six bacterial strains associated with vaginal health, and a second generated from over 1,000 mid-vaginal samples collected as part of the Vaginal Human Microbiome Project at Virginia Commonwealth University. In both datasets, STIRRUPS, used in conjunction with the Vaginal 16S rDNA Reference Database, classified more than 95% of processed reads to a species-level taxon using a 97% global identity threshold for assignment.

CONCLUSIONS: This database and method provide accurate species-level classifications of metagenomic 16S rDNA sequence reads that will be useful for analysis and comparison of microbiome profiles from vaginal samples. STIRRUPS can be used to classify 16S rDNA sequence reads from other ecological niches if an appropriate reference database of 16S rDNA sequences is available.},
}

Algorithms
Bacteria/*classification/genetics
Databases, Genetic
Female
Humans
*Metagenome
RNA, Ribosomal, 16S/genetics
Vagina/*microbiology

@article {pmid23296358,
year = {2013},
author = {Foxman, B and Rosenthal, M},
title = {Implications of the human microbiome project for epidemiology.},
journal = {American journal of epidemiology},
volume = {177},
number = {3},
pages = {197-201},
pmid = {23296358},
issn = {1476-6256},
support = {R01 DE014899/DE/NIDCR NIH HHS/United States ; T32 AI049816/AI/NIAID NIH HHS/United States ; },
mesh = {Bacteria/genetics/isolation & purification ; Epidemiology/*organization & administration ; Fungi/genetics/isolation & purification ; Humans ; *Metagenome ; Microbial Consortia ; Polymerase Chain Reaction ; Risk Factors ; Time Factors ; Viruses/genetics/isolation & purification ; },
abstract = {The structure and function of microorganisms that live in and on us, the human microbiota, are a tremendous resource. Microbiota may help to explain individual variability in health outcomes and be a source of new biomarkers for environmental exposures and of novel prognostic and diagnostic indicators. The increase in availability of low-cost, high-throughput techniques makes it relatively straightforward to include microbiota assessments in epidemiologic studies. With the recent joint publications of the findings of the Human Microbiome Consortium and related studies, the consequent surge of interest in microbiome research, and remarkable media attention, the time is ripe for epidemiologists to contribute their expertise to and translate results of microbiota research for population health.},
}

Bacteria/genetics/isolation & purification
Epidemiology/*organization & administration
Fungi/genetics/isolation & purification
Humans
*Metagenome
Microbial Consortia
Polymerase Chain Reaction
Risk Factors
Time Factors
Viruses/genetics/isolation & purification

@article {pmid23326225,
year = {2013},
author = {Koren, O and Knights, D and Gonzalez, A and Waldron, L and Segata, N and Knight, R and Huttenhower, C and Ley, RE},
title = {A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets.},
journal = {PLoS computational biology},
volume = {9},
number = {1},
pages = {e1002863},
pmid = {23326225},
issn = {1553-7358},
support = {HG4872/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; },
mesh = {Bacteria/*classification/genetics ; Biodiversity ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; },
abstract = {Recent analyses of human-associated bacterial diversity have categorized individuals into 'enterotypes' or clusters based on the abundances of key bacterial genera in the gut microbiota. There is a lack of consensus, however, on the analytical basis for enterotypes and on the interpretation of these results. We tested how the following factors influenced the detection of enterotypes: clustering methodology, distance metrics, OTU-picking approaches, sequencing depth, data type (whole genome shotgun (WGS) vs.16S rRNA gene sequence data), and 16S rRNA region. We included 16S rRNA gene sequences from the Human Microbiome Project (HMP) and from 16 additional studies and WGS sequences from the HMP and MetaHIT. In most body sites, we observed smooth abundance gradients of key genera without discrete clustering of samples. Some body habitats displayed bimodal (e.g., gut) or multimodal (e.g., vagina) distributions of sample abundances, but not all clustering methods and workflows accurately highlight such clusters. Because identifying enterotypes in datasets depends not only on the structure of the data but is also sensitive to the methods applied to identifying clustering strength, we recommend that multiple approaches be used and compared when testing for enterotypes.},
}

Bacteria/*classification/genetics
Biodiversity
Humans
*Metagenome
RNA, Ribosomal, 16S/genetics

@article {pmid23392441,
year = {2013},
author = {Lozupone, C and Cota-Gomez, A and Palmer, BE and Linderman, DJ and Charlson, ES and Sodergren, E and Mitreva, M and Abubucker, S and Martin, J and Yao, G and Campbell, TB and Flores, SC and Ackerman, G and Stombaugh, J and Ursell, L and Beck, JM and Curtis, JL and Young, VB and Lynch, SV and Huang, L and Weinstock, GM and Knox, KS and Twigg, H and Morris, A and Ghedin, E and Bushman, FD and Collman, RG and Knight, R and Fontenot, AP and , },
title = {Widespread colonization of the lung by Tropheryma whipplei in HIV infection.},
journal = {American journal of respiratory and critical care medicine},
volume = {187},
number = {10},
pages = {1110-1117},
pmid = {23392441},
issn = {1535-4970},
support = {U01 AI035042/AI/NIAID NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; DK090285/DK/NIDDK NIH HHS/United States ; AI35004/AI/NIAID NIH HHS/United States ; AI35042/AI/NIAID NIH HHS/United States ; U01 HL098961/HL/NHLBI NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01 AI035004/AI/NIAID NIH HHS/United States ; AI35039/AI/NIAID NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; U01 AI075410/AI/NIAID NIH HHS/United States ; AI35043/AI/NIAID NIH HHS/United States ; AI34993/AI/NIAID NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; HL098957/HL/NHLBI NIH HHS/United States ; HL098962/HL/NHLBI NIH HHS/United States ; UL1 RR024131/RR/NCRR NIH HHS/United States ; HL087713/HL/NHLBI NIH HHS/United States ; HD32632/HD/NICHD NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; HL102245/HL/NHLBI NIH HHS/United States ; UL1TR000005/TR/NCATS NIH HHS/United States ; K01 DK090285/DK/NIDDK NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; K24 HL102245/HL/NHLBI NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; AI35040/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; AI34989/AI/NIAID NIH HHS/United States ; U01 HL098957/HL/NHLBI NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; UL1-RR025005/RR/NCRR NIH HHS/United States ; R01 HL090339/HL/NHLBI NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; HL098961/HL/NHLBI NIH HHS/United States ; HL98996/HL/NHLBI NIH HHS/United States ; R01 HL090335/HL/NHLBI NIH HHS/United States ; AI34994/AI/NIAID NIH HHS/United States ; U01 AI035043/AI/NIAID NIH HHS/United States ; HL090339/HL/NHLBI NIH HHS/United States ; AI045008/AI/NIAID NIH HHS/United States ; HL098964/HL/NHLBI NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; HL098960/HL/NHLBI NIH HHS/United States ; AI35041/AI/NIAID NIH HHS/United States ; U01 AI035039/AI/NIAID NIH HHS/United States ; U01AI42590/AI/NIAID NIH HHS/United States ; HL090335/HL/NHLBI NIH HHS/United States ; U01 HL098996/HL/NHLBI NIH HHS/United States ; AI31834/AI/NIAID NIH HHS/United States ; AI075410/AI/NIAID NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; },
mesh = {Cohort Studies ; HIV Infections/*complications ; Humans ; Longitudinal Studies ; Lung/*microbiology ; *Tropheryma ; Whipple Disease/*complications/*microbiology ; },
abstract = {RATIONALE: Lung infections caused by opportunistic or virulent pathogens are a principal cause of morbidity and mortality in HIV infection. It is unknown whether HIV infection leads to changes in basal lung microflora, which may contribute to chronic pulmonary complications that increasingly are being recognized in individuals infected with HIV.

OBJECTIVES: To determine whether the immunodeficiency associated with HIV infection resulted in alteration of the lung microbiota.

METHODS: We used 16S ribosomal RNA targeted pyrosequencing and shotgun metagenomic sequencing to analyze bacterial gene sequences in bronchoalveolar lavage (BAL) and mouths of 82 HIV-positive and 77 HIV-negative subjects.

MEASUREMENTS AND MAIN RESULTS: Sequences representing Tropheryma whipplei, the etiologic agent of Whipple's disease, were significantly more frequent in BAL of HIV-positive compared with HIV-negative individuals. T. whipplei dominated the community (>50% of sequence reads) in 11 HIV-positive subjects, but only 1 HIV-negative individual (13.4 versus 1.3%; P = 0.0018). In 30 HIV-positive individuals sampled longitudinally, antiretroviral therapy resulted in a significantly reduced relative abundance of T. whipplei in the lung. Shotgun metagenomic sequencing was performed on eight BAL samples dominated by T. whipplei 16S ribosomal RNA. Whole genome assembly of pooled reads showed that uncultured lung-derived T. whipplei had similar gene content to two isolates obtained from subjects with Whipple's disease.

CONCLUSIONS: Asymptomatic subjects with HIV infection have unexpected colonization of the lung by T. whipplei, which is reduced by effective antiretroviral therapy and merits further study for a potential pathogenic role in chronic pulmonary complications of HIV infection.},
}

Cohort Studies
HIV Infections/*complications
Humans
Longitudinal Studies
Lung/*microbiology
*Tropheryma
Whipple Disease/*complications/*microbiology

@article {pmid23400224,
year = {2013},
author = {Douglas-Escobar, M and Elliott, E and Neu, J},
title = {Effect of intestinal microbial ecology on the developing brain.},
journal = {JAMA pediatrics},
volume = {167},
number = {4},
pages = {374-379},
doi = {10.1001/jamapediatrics.2013.497},
pmid = {23400224},
issn = {2168-6211},
support = {R01 HD 059143/HD/NICHD NIH HHS/United States ; },
mesh = {Animals ; Brain/growth & development/*physiology ; Child ; Child Development Disorders, Pervasive/epidemiology/microbiology ; Comorbidity ; Enteric Nervous System/physiology ; Gastrointestinal Diseases/epidemiology ; Humans ; Infant, Newborn ; Infant, Premature/physiology ; Intestines/immunology/*microbiology/*physiology ; Metagenome/immunology/*physiology ; Toll-Like Receptors/physiology ; },
abstract = {The mammalian gastrointestinal tract harbors a highly diverse microbial population that plays a major role in nutrition, metabolism, protection against pathogens, and development of the immune system. It is estimated that at least 1000 different bacterial species cohabit the human intestinal tract. Most recently, the Human Microbiome Project, using new genomic technologies, has started a catalog of specific microbiome composition and its correlation with health and specific diseases. Herein we provide a brief review of the intestinal microbiome, with a focus on new studies showing that there is an important link between the microbes that inhabit the intestinal tract and the developing brain. With future research, an understanding of this link may help us to treat various neurobehavioral problems such as autism, schizophrenia, and anxiety.},
}

Animals
Brain/growth & development/*physiology
Child
Child Development Disorders, Pervasive/epidemiology/microbiology
Comorbidity
Enteric Nervous System/physiology
Gastrointestinal Diseases/epidemiology
Humans
Infant, Newborn
Infant, Premature/physiology
Intestines/immunology/*microbiology/*physiology
Metagenome/immunology/*physiology
Toll-Like Receptors/physiology

@article {pmid23401286,
year = {2013},
author = {Devaraj, S and Hemarajata, P and Versalovic, J},
title = {The human gut microbiome and body metabolism: implications for obesity and diabetes.},
journal = {Clinical chemistry},
volume = {59},
number = {4},
pages = {617-628},
pmid = {23401286},
issn = {1530-8561},
support = {R01 DK065075-01/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; P30 DK56338-06A2/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; R01 AT004326-01A1/AT/NCCIH NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; },
mesh = {Amino Acids/metabolism ; Animals ; Carbohydrate Metabolism ; Diabetes Mellitus/metabolism/*microbiology ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; *Metagenome ; Obesity/*microbiology ; },
abstract = {BACKGROUND: Obesity, metabolic syndrome, and type 2 diabetes are major public health challenges. Recently, interest has surged regarding the possible role of the intestinal microbiota as potential novel contributors to the increased prevalence of these 3 disorders.

CONTENT: Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut. Current evidence suggests that the gut microbiota affect nutrient acquisition, energy harvest, and a myriad of host metabolic pathways.

CONCLUSION: Advances in the Human Microbiome Project and human metagenomics research will lead the way toward a greater understanding of the importance and role of the gut microbiome in metabolic disorders such as obesity, metabolic syndrome, and diabetes.},
}

Amino Acids/metabolism
Animals
Carbohydrate Metabolism
Diabetes Mellitus/metabolism/*microbiology
Humans
Intestinal Mucosa/metabolism
Intestines/*microbiology
*Metagenome
Obesity/*microbiology

@article {pmid23406581,
year = {2013},
author = {Renko, J and Koskela, KA and Lepp, PW and Oksala, N and Levula, M and Lehtimäki, T and Solakivi, T and Kunnas, T and Nikkari, S and Nikkari, ST},
title = {Bacterial DNA signatures in carotid atherosclerosis represent both commensals and pathogens of skin origin.},
journal = {European journal of dermatology : EJD},
volume = {23},
number = {1},
pages = {53-58},
doi = {10.1684/ejd.2012.1908},
pmid = {23406581},
issn = {1952-4013},
mesh = {Actinobacteria/*isolation & purification ; Aged ; Aged, 80 and over ; Carotid Artery Diseases/*microbiology ; DNA, Bacterial/*isolation & purification ; DNA, Ribosomal ; Female ; Humans ; Male ; *Metagenome ; Middle Aged ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Skin/*microbiology ; },
abstract = {Infectious agents have been suggested to be involved in atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile carotid artery endarterectomy plaques of patients with carotid atherosclerosis. Eighty partial bacterial 16S rDNA nucleotide sequences from eight patients were studied. Furthermore, 34 clones representing 21 bacterial sequence-types from the reagents used for DNA extraction and PCR amplification were determined. After subtraction of these potential methodological contaminants, 23 bacterial sequence-types were considered as clinically relevant findings. The most prominent phylum, Actinobacteria, accounted for 74% of these relevant sequences. Furthermore, according to the Human Microbiome project database, interestingly, nearly all (94%) of the sequences were associated with the human skin microbiome.},
}

Actinobacteria/*isolation & purification
Aged
Aged, 80 and over
Carotid Artery Diseases/*microbiology
DNA, Bacterial/*isolation & purification
DNA, Ribosomal
Female
Humans
Male
*Metagenome
Middle Aged
Polymerase Chain Reaction
Sequence Analysis, DNA
Skin/*microbiology

@article {pmid23408395,
year = {2012},
author = {Mead, DA and Lucas, S and Copeland, A and Lapidus, A and Cheng, JF and Bruce, DC and Goodwin, LA and Pitluck, S and Chertkov, O and Zhang, X and Detter, JC and Han, CS and Tapia, R and Land, M and Hauser, LJ and Chang, YJ and Kyrpides, NC and Ivanova, NN and Ovchinnikova, G and Woyke, T and Brumm, C and Hochstein, R and Schoenfeld, T and Brumm, P},
title = {Complete Genome Sequence of Paenibacillus strain Y4.12MC10, a Novel Paenibacillus lautus strain Isolated from Obsidian Hot Spring in Yellowstone National Park.},
journal = {Standards in genomic sciences},
volume = {6},
number = {3},
pages = {381-400},
pmid = {23408395},
issn = {1944-3277},
abstract = {Paenibacillus sp.Y412MC10 was one of a number of organisms isolated from Obsidian Hot Spring, Yellowstone National Park, Montana, USA under permit from the National Park Service. The isolate was initially classified as a Geobacillus sp. Y412MC10 based on its isolation conditions and similarity to other organisms isolated from hot springs at Yellowstone National Park. Comparison of 16 S rRNA sequences within the Bacillales indicated that Geobacillus sp.Y412MC10 clustered with Paenibacillus species, and the organism was most closely related to Paenibacillus lautus. Lucigen Corp. prepared genomic DNA and the genome was sequenced, assembled, and annotated by the DOE Joint Genome Institute. The genome sequence was deposited at the NCBI in October 2009 (NC_013406). The genome of Paenibacillus sp. Y412MC10 consists of one circular chromosome of 7,121,665 bp with an average G+C content of 51.2%. Comparison to other Paenibacillus species shows the organism lacks nitrogen fixation, antibiotic production and social interaction genes reported in other paenibacilli. The Y412MC10 genome shows a high level of synteny and homology to the draft sequence of Paenibacillus sp. HGF5, an organism from the Human Microbiome Project (HMP) Reference Genomes. This, combined with genomic CAZyme analysis, suggests an intestinal, rather than environmental origin for Y412MC10.},
}

@article {pmid23418187,
year = {2013},
author = {Klingenberg, H and Aßhauer, KP and Lingner, T and Meinicke, P},
title = {Protein signature-based estimation of metagenomic abundances including all domains of life and viruses.},
journal = {Bioinformatics (Oxford, England)},
volume = {29},
number = {8},
pages = {973-980},
pmid = {23418187},
issn = {1367-4811},
mesh = {DNA, Archaeal/analysis ; DNA, Viral/analysis ; Humans ; Metagenome ; Metagenomics/*methods ; Phylogeny ; *Protein Structure, Tertiary ; },
abstract = {MOTIVATION: Metagenome analysis requires tools that can estimate the taxonomic abundances in anonymous sequence data over the whole range of biological entities. Because there is usually no prior knowledge about the data composition, not only all domains of life but also viruses have to be included in taxonomic profiling. Such a full-range approach, however, is difficult to realize owing to the limited coverage of available reference data. In particular, archaea and viruses are generally not well represented by current genome databases.

RESULTS: We introduce a novel approach to taxonomic profiling of metagenomes that is based on mixture model analysis of protein signatures. Our results on simulated and real data reveal the difficulties of the existing methods when measuring achaeal or viral abundances and show the overall good profiling performance of the protein-based mixture model. As an application example, we provide a large-scale analysis of data from the Human Microbiome Project. This demonstrates the utility of our method as a first instance profiling tool for a fast estimate of the community structure.

AVAILABILITY: http://gobics.de/TaxyPro.

SUPPLEMENTARY INFORMATION: Supplementary Material is available at Bioinformatics online.},
}

DNA, Archaeal/analysis
DNA, Viral/analysis
Humans
Metagenome
Metagenomics/*methods
Phylogeny
*Protein Structure, Tertiary

@article {pmid23431991,
year = {2013},
author = {Bakhtiar, SM and LeBlanc, JG and Salvucci, E and Ali, A and Martin, R and Langella, P and Chatel, JM and Miyoshi, A and Bermúdez-Humarán, LG and Azevedo, V},
title = {Implications of the human microbiome in inflammatory bowel diseases.},
journal = {FEMS microbiology letters},
volume = {342},
number = {1},
pages = {10-17},
doi = {10.1111/1574-6968.12111},
pmid = {23431991},
issn = {1574-6968},
mesh = {*Biota ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammatory Bowel Diseases/*microbiology ; *Metagenome ; },
abstract = {The study of the human microbiome or community of microorganisms and collection of genomes found in the human body is one of the fastest growing research areas because many diseases are reported to be associated with microbiome imbalance or dysbiosis. With the improvement in novel sequencing techniques, researchers are now generating millions of sequences of different sites from the human body and evaluating specific differences in microbial communities. The importance of microbiome constituency is so relevant that several consortia like the Human Microbiome project (HMP) and Metagenomics of the Human Intestinal Tract (MetaHIT) project are focusing mainly on the human microbiome. The aim of this review is to highlight points of research in this field, mainly focusing on particular factors that modulate the microbiome and important insights into its potential impact on our health and well-being.},
}

*Biota
High-Throughput Nucleotide Sequencing
Humans
Inflammatory Bowel Diseases/*microbiology
*Metagenome

@article {pmid23444796,
year = {2012},
author = {Błaszkowska, J and Wójcik, A},
title = {Current problems concerning parasitology and mycology with regard to diseases of the skin and its appendages.},
journal = {Annals of parasitology},
volume = {58},
number = {3},
pages = {111-123},
pmid = {23444796},
issn = {2299-0631},
mesh = {Animals ; Dermatomycoses/diagnosis/epidemiology/therapy/transmission ; Humans ; Mycoses/*diagnosis/epidemiology/*therapy/transmission ; Parasitic Diseases/*diagnosis/epidemiology/*therapy/transmission ; Zoonoses/microbiology/parasitology/transmission ; },
abstract = {Current issues concerning Parasitology and Mycology with regard to diseases of the skin and its appendages are presented. Aspects of diagnostics, clinical picture and therapy of skin and nail mycoses, as well as difficulties in the diagnosis and treatment of both native parasitoses (toxoplasmosis) and imported human tropical parasitoses (malaria, filariosis) have been emphasised. The clinical importance of environmental mould fungi in nosocomial infections and fungal meningitis, as well as selected properties of fungi isolated from patients with head and neck neoplasms treated by radiotherapy are discussed. Other mycological topics include the characteristics of newly-synthesized thiosemicarbazides and thiadiazoles as potential drugs against toxoplasmosis and their biological activity against Toxoplasma gondii tachyzoites, selected molecular mechanisms of resistance to azoles, Candida albicans strains and a new tool (barcoding DNA) for describing the biodiversity of potential allergenic molds. The importance of environmental factors in pathogenesis of mycoses and parasitoses is noted. The characteristics of pathogenic fungi isolated from natural ponds in Bialystok and potentially pathogenic yeast-like fungi isolated from children's recreation areas in Lodz are presented. The ongoing problem of anthropozoonoses is considered, as are the roles of stray cats and dogs in contaminating soil with the developing forms of intestinal parasites. The characteristics of the human microbiome, including population composition, activity and their importance in normal human physiology, are presented, as are the major goals of the Human Microbiome Project initiated by National Institutes of Health (NIH).},
}

Animals
Dermatomycoses/diagnosis/epidemiology/therapy/transmission
Humans
Mycoses/*diagnosis/epidemiology/*therapy/transmission
Parasitic Diseases/*diagnosis/epidemiology/*therapy/transmission
Zoonoses/microbiology/parasitology/transmission

@article {pmid23491408,
year = {2013},
author = {Morris, A and Beck, JM and Schloss, PD and Campbell, TB and Crothers, K and Curtis, JL and Flores, SC and Fontenot, AP and Ghedin, E and Huang, L and Jablonski, K and Kleerup, E and Lynch, SV and Sodergren, E and Twigg, H and Young, VB and Bassis, CM and Venkataraman, A and Schmidt, TM and Weinstock, GM and , },
title = {Comparison of the respiratory microbiome in healthy nonsmokers and smokers.},
journal = {American journal of respiratory and critical care medicine},
volume = {187},
number = {10},
pages = {1067-1075},
pmid = {23491408},
issn = {1535-4970},
support = {U01 AI035004/AI/NIAID NIH HHS/United States ; U01-AI-35004/AI/NIAID NIH HHS/United States ; R01 HL090335/HL/NHLBI NIH HHS/United States ; U01-AI-35039/AI/NIAID NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; U01HL098958/HL/NHLBI NIH HHS/United States ; U01 AI035042/AI/NIAID NIH HHS/United States ; T32 HL007749/HL/NHLBI NIH HHS/United States ; K24HL087713/HL/NHLBI NIH HHS/United States ; U01HL098964/HL/NHLBI NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; U01-AI-35043/AI/NIAID NIH HHS/United States ; U01-AI-35042/AI/NIAID NIH HHS/United States ; U01-AI-42590/AI/NIAID NIH HHS/United States ; U01 HL098958/HL/NHLBI NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01-HD-32632/HD/NICHD NIH HHS/United States ; U01HL098960/HL/NHLBI NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; U01HL098996/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; R01 HL090342/HL/NHLBI NIH HHS/United States ; UL1 RR024131/RR/NCRR NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; U01HL98961/HL/NHLBI NIH HHS/United States ; UL1TR000005/TR/NCATS NIH HHS/United States ; U01-AI-35041/AI/NIAID NIH HHS/United States ; U01-AI-34994/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; K24 HL102245/HL/NHLBI NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; R0100417746//PHS HHS/United States ; U01-AI-31834/AI/NIAID NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; U01 HL098961/HL/NHLBI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; UL1-RR025005/RR/NCRR NIH HHS/United States ; U01-AI-35040/AI/NIAID NIH HHS/United States ; R01 HL090339/HL/NHLBI NIH HHS/United States ; UL1TR000004/TR/NCATS NIH HHS/United States ; R01HL090342/HL/NHLBI NIH HHS/United States ; U01 AI035043/AI/NIAID NIH HHS/United States ; R01HL090335/HL/NHLBI NIH HHS/United States ; U01-AI-34993/AI/NIAID NIH HHS/United States ; R01HL090339/HL/NHLBI NIH HHS/United States ; U01 AI035039/AI/NIAID NIH HHS/United States ; U01 HL098996/HL/NHLBI NIH HHS/United States ; U01HL098962/HL/NHLBI NIH HHS/United States ; U01-AI-34989/AI/NIAID NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bronchoalveolar Lavage Fluid/microbiology ; Cohort Studies ; Female ; Humans ; Lung/microbiology ; Male ; *Metagenome ; Middle Aged ; Mouth/microbiology ; Prospective Studies ; Reference Values ; Respiratory System/*microbiology ; Sequence Analysis, DNA/methods ; *Smoking ; Young Adult ; },
abstract = {RATIONALE: Results from 16S rDNA-encoding gene sequence-based, culture-independent techniques have led to conflicting conclusions about the composition of the lower respiratory tract microbiome.

OBJECTIVES: To compare the microbiome of the upper and lower respiratory tract in healthy HIV-uninfected nonsmokers and smokers in a multicenter cohort.

METHODS: Participants were nonsmokers and smokers without significant comorbidities. Oral washes and bronchoscopic alveolar lavages were collected in a standardized manner. Sequence analysis of bacterial 16S rRNA-encoding genes was performed, and the neutral model in community ecology was used to identify bacteria that were the most plausible members of a lung microbiome.

MEASUREMENTS AND MAIN RESULTS: Sixty-four participants were enrolled. Most bacteria identified in the lung were also in the mouth, but specific bacteria such as Enterobacteriaceae, Haemophilus, Methylobacterium, and Ralstonia species were disproportionally represented in the lungs compared with values predicted by the neutral model. Tropheryma was also in the lung, but not the mouth. Mouth communities differed between nonsmokers and smokers in species such as Porphyromonas, Neisseria, and Gemella, but lung bacterial populations did not.

CONCLUSIONS: This study is the largest to examine composition of the lower respiratory tract microbiome in healthy individuals and the first to use the neutral model to compare the lung to the mouth. Specific bacteria appear in significantly higher abundance in the lungs than would be expected if they originated from the mouth, demonstrating that the lung microbiome does not derive entirely from the mouth. The mouth microbiome differs in nonsmokers and smokers, but lung communities were not significantly altered by smoking.},
}

Adolescent
Adult
Aged
Aged, 80 and over
Bronchoalveolar Lavage Fluid/microbiology
Cohort Studies
Female
Humans
Lung/microbiology
Male
*Metagenome
Middle Aged
Mouth/microbiology
Prospective Studies
Reference Values
Respiratory System/*microbiology
Sequence Analysis, DNA/methods
*Smoking
Young Adult

@article {pmid23509275,
year = {2013},
author = {Campbell, JH and O'Donoghue, P and Campbell, AG and Schwientek, P and Sczyrba, A and Woyke, T and Söll, D and Podar, M},
title = {UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {110},
number = {14},
pages = {5540-5545},
pmid = {23509275},
issn = {1091-6490},
support = {R01 GM022854/GM/NIGMS NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; R37 GM022854/GM/NIGMS NIH HHS/United States ; GM22854/GM/NIGMS NIH HHS/United States ; },
mesh = {Bacteria/*genetics ; Base Sequence ; Codon, Terminator/*genetics ; Flow Cytometry ; Genetic Code/*genetics ; Genetic Variation ; Glycine/*genetics ; Humans ; Metagenome/*genetics ; Molecular Sequence Data ; Mouth/*microbiology ; Nucleic Acid Amplification Techniques ; Sequence Analysis, DNA ; },
abstract = {The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA(Gly)UCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA(Gly)UCA with glycine in vitro with similar activity compared with normal tRNA(Gly)UCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNA(Gly)UCA in Escherichia coli yields significant β-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.},
}

Bacteria/*genetics
Base Sequence
Codon, Terminator/*genetics
Flow Cytometry
Genetic Code/*genetics
Genetic Variation
Glycine/*genetics
Humans
Metagenome/*genetics
Molecular Sequence Data
Mouth/*microbiology
Nucleic Acid Amplification Techniques
Sequence Analysis, DNA

@article {pmid23587224,
year = {2012},
author = {McDonald, D and Clemente, JC and Kuczynski, J and Rideout, JR and Stombaugh, J and Wendel, D and Wilke, A and Huse, S and Hufnagle, J and Meyer, F and Knight, R and Caporaso, JG},
title = {The Biological Observation Matrix (BIOM) format or: how I learned to stop worrying and love the ome-ome.},
journal = {GigaScience},
volume = {1},
number = {1},
pages = {7},
pmid = {23587224},
issn = {2047-217X},
abstract = {BACKGROUND: We present the Biological Observation Matrix (BIOM, pronounced "biome") format: a JSON-based file format for representing arbitrary observation by sample contingency tables with associated sample and observation metadata. As the number of categories of comparative omics data types (collectively, the "ome-ome") grows rapidly, a general format to represent and archive this data will facilitate the interoperability of existing bioinformatics tools and future meta-analyses.

FINDINGS: The BIOM file format is supported by an independent open-source software project (the biom-format project), which initially contains Python objects that support the use and manipulation of BIOM data in Python programs, and is intended to be an open development effort where developers can submit implementations of these objects in other programming languages.

CONCLUSIONS: The BIOM file format and the biom-format project are steps toward reducing the "bioinformatics bottleneck" that is currently being experienced in diverse areas of biological sciences, and will help us move toward the next phase of comparative omics where basic science is translated into clinical and environmental applications. The BIOM file format is currently recognized as an Earth Microbiome Project Standard, and as a Candidate Standard by the Genomic Standards Consortium.},
}

@article {pmid23671663,
year = {2013},
author = {Li, K and Bihan, M and Methé, BA},
title = {Analyses of the stability and core taxonomic memberships of the human microbiome.},
journal = {PloS one},
volume = {8},
number = {5},
pages = {e63139},
pmid = {23671663},
issn = {1932-6203},
support = {U54 AI084844/AI/NIAID NIH HHS/United States ; AI084844/AI/NIAID NIH HHS/United States ; },
mesh = {Bacteria/classification/*genetics ; Feces/microbiology ; Female ; Humans ; *Microbiota ; Molecular Typing ; Mouth/microbiology ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/microbiology ; Vagina/microbiology ; },
abstract = {Analyses of the taxonomic diversity associated with the human microbiome continue to be an area of great importance. The study of the nature and extent of the commonly shared taxa ("core"), versus those less prevalent, establishes a baseline for comparing healthy and diseased groups by quantifying the variation among people, across body habitats and over time. The National Institutes of Health (NIH) sponsored Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine and better define what constitutes the taxonomic core within and across body habitats and individuals through pyrosequencing-based profiling of 16S rRNA gene sequences from oral, skin, distal gut (stool), and vaginal body habitats from over 200 healthy individuals. A two-parameter model is introduced to quantitatively identify the core taxonomic members of each body habitat's microbiota across the healthy cohort. Using only cutoffs for taxonomic ubiquity and abundance, core taxonomic members were identified for each of the 18 body habitats and also for the 4 higher-level body regions. Although many microbes were shared at low abundance, they exhibited a relatively continuous spread in both their abundance and ubiquity, as opposed to a more discretized separation. The numbers of core taxa members in the body regions are comparatively small and stable, reflecting the relatively high, but conserved, interpersonal variability within the cohort. Core sizes increased across the body regions in the order of: vagina, skin, stool, and oral cavity. A number of "minor" oral taxonomic core were also identified by their majority presence across the cohort, but with relatively low and stable abundances. A method for quantifying the difference between two cohorts was introduced and applied to samples collected on a second visit, revealing that over time, the oral, skin, and stool body regions tended to be more transient in their taxonomic structure than the vaginal body region.},
}

Bacteria/classification/*genetics
Feces/microbiology
Female
Humans
*Microbiota
Molecular Typing
Mouth/microbiology
Phylogeny
RNA, Bacterial/genetics
RNA, Ribosomal, 16S/genetics
Sequence Analysis, DNA
Skin/microbiology
Vagina/microbiology

@article {pmid23678462,
year = {2012},
author = {Eslami, S and Barzgari, Z and Saliani, N and Saeedi, N and Barzegari, A},
title = {Annual fasting; the early calories restriction for cancer prevention.},
journal = {BioImpacts : BI},
volume = {2},
number = {4},
pages = {213-215},
pmid = {23678462},
issn = {2228-5652},
abstract = {Essentially, people's diet and nutritional status has been changed substantially worldwide and several lines of evidence suggest that these changes are to the detriment of their health. Additionally, it has been well documented that unhealthy diet especially the fast foods, untraditional foods or bad-eating-habits influence the human gut microbiome. The gut microbiota shapes immune responses during human life and affects his/her metabolomic profiles. Furthermore, many studies highlight the molecular pathways that mediate host and symbiont interactions that regulate proper immune function and prevention of cancer in the body. Intriguingly, if cancer forms in a human body due to the weakness of immune system in detriment of microbiome, the removal of cancer stem cells can be carried out through early Calories Restriction with Annual Fasting (AF) before tumor development or progress. Besides, fasting can balance the gut microbiome for enhancement of immune system against cancer formation.},
}

@article {pmid23704890,
year = {2013},
author = {Boyd, PW and Rynearson, TA and Armstrong, EA and Fu, F and Hayashi, K and Hu, Z and Hutchins, DA and Kudela, RM and Litchman, E and Mulholland, MR and Passow, U and Strzepek, RF and Whittaker, KA and Yu, E and Thomas, MK},
title = {Marine phytoplankton temperature versus growth responses from polar to tropical waters--outcome of a scientific community-wide study.},
journal = {PloS one},
volume = {8},
number = {5},
pages = {e63091},
pmid = {23704890},
issn = {1932-6203},
mesh = {Aquatic Organisms/*growth & development/isolation & purification ; *Ecosystem ; Humans ; Oceans and Seas ; Phytoplankton/*growth & development/isolation & purification ; Species Specificity ; *Temperature ; *Tropical Climate ; Water ; },
abstract = {"It takes a village to finish (marine) science these days" Paraphrased from Curtis Huttenhower (the Human Microbiome project) The rapidity and complexity of climate change and its potential effects on ocean biota are challenging how ocean scientists conduct research. One way in which we can begin to better tackle these challenges is to conduct community-wide scientific studies. This study provides physiological datasets fundamental to understanding functional responses of phytoplankton growth rates to temperature. While physiological experiments are not new, our experiments were conducted in many laboratories using agreed upon protocols and 25 strains of eukaryotic and prokaryotic phytoplankton isolated across a wide range of marine environments from polar to tropical, and from nearshore waters to the open ocean. This community-wide approach provides both comprehensive and internally consistent datasets produced over considerably shorter time scales than conventional individual and often uncoordinated lab efforts. Such datasets can be used to parameterise global ocean model projections of environmental change and to provide initial insights into the magnitude of regional biogeographic change in ocean biota in the coming decades. Here, we compare our datasets with a compilation of literature data on phytoplankton growth responses to temperature. A comparison with prior published data suggests that the optimal temperatures of individual species and, to a lesser degree, thermal niches were similar across studies. However, a comparison of the maximum growth rate across studies revealed significant departures between this and previously collected datasets, which may be due to differences in the cultured isolates, temporal changes in the clonal isolates in cultures, and/or differences in culture conditions. Such methodological differences mean that using particular trait measurements from the prior literature might introduce unknown errors and bias into modelling projections. Using our community-wide approach we can reduce such protocol-driven variability in culture studies, and can begin to address more complex issues such as the effect of multiple environmental drivers on ocean biota.},
}

Aquatic Organisms/*growth & development/isolation & purification
*Ecosystem
Humans
Oceans and Seas
Phytoplankton/*growth & development/isolation & purification
Species Specificity
*Temperature
*Tropical Climate
Water

@article {pmid23734710,
year = {2013},
author = {Ander, C and Schulz-Trieglaff, OB and Stoye, J and Cox, AJ},
title = {metaBEETL: high-throughput analysis of heterogeneous microbial populations from shotgun DNA sequences.},
journal = {BMC bioinformatics},
volume = {14 Suppl 5},
number = {Suppl 5},
pages = {S2},
pmid = {23734710},
issn = {1471-2105},
mesh = {Algorithms ; Environmental Microbiology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; *Microbiota ; Phylogeny ; Sequence Analysis, DNA/*methods ; },
abstract = {Environmental shotgun sequencing (ESS) has potential to give greater insight into microbial communities than targeted sequencing of 16S regions, but requires much higher sequence coverage. The advent of next-generation sequencing has made it feasible for the Human Microbiome Project and other initiatives to generate ESS data on a large scale, but computationally efficient methods for analysing such data sets are needed.Here we present metaBEETL, a fast taxonomic classifier for environmental shotgun sequences. It uses a Burrows-Wheeler Transform (BWT) index of the sequencing reads and an indexed database of microbial reference sequences. Unlike other BWT-based tools, our method has no upper limit on the number or the total size of the reference sequences in its database. By capturing sequence relationships between strains, our reference index also allows us to classify reads which are not unique to an individual strain but are nevertheless specific to some higher phylogenetic order.Tested on datasets with known taxonomic composition, metaBEETL gave results that are competitive with existing similarity-based tools: due to normalization steps which other classifiers lack, the taxonomic profile computed by metaBEETL closely matched the true environmental profile. At the same time, its moderate running time and low memory footprint allow metaBEETL to scale well to large data sets.Code to construct the BWT indexed database and for the taxonomic classification is part of the BEETL library, available as a github repository at git@github.com:BEETL/BEETL.git.},
}

Algorithms
Environmental Microbiology
High-Throughput Nucleotide Sequencing/*methods
Humans
Metagenomics/*methods
*Microbiota
Phylogeny
Sequence Analysis, DNA/*methods

@article {pmid23802897,
year = {2013},
author = {Hoffmann, DE and Fortenberry, JD and Ravel, J},
title = {Are changes to the common rule necessary to address evolving areas of research? A case study focusing on the human microbiome project.},
journal = {The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics},
volume = {41},
number = {2},
pages = {454-469},
pmid = {23802897},
issn = {1748-720X},
support = {R01 HG005171/HG/NHGRI NIH HHS/United States ; },
mesh = {Human Experimentation/*legislation & jurisprudence ; Humans ; *Metagenome ; National Institutes of Health (U.S.) ; Patient Selection ; Research Subjects/*legislation & jurisprudence ; Social Stigma ; United States ; },
abstract = {This article examines ways in which research conducted under the Human Microbiome Project, an effort to establish a "reference catalogue" of the micro-organisms present in the human body and determine how changes in those micro-organisms affect health and disease, raise challenging issues for regulation of human subject research. The article focuses on issues related to subject selection and recruitment, group stigma, and informational risks, and explores whether: (1) the Common Rule or proposed changes to the Rule adequately address these issues and (2) the Common Rule is the most appropriate vehicle to provide regulatory oversight and guidance on these topics.},
}

Human Experimentation/*legislation & jurisprudence
Humans
*Metagenome
National Institutes of Health (U.S.)
Patient Selection
Research Subjects/*legislation & jurisprudence
Social Stigma
United States

@article {pmid23908833,
year = {2012},
author = {Solt, I and Cohavy, O},
title = {The great obstetrical syndromes and the human microbiome-a new frontier.},
journal = {Rambam Maimonides medical journal},
volume = {3},
number = {2},
pages = {e0009},
pmid = {23908833},
issn = {2076-9172},
abstract = {Over the last two decades, advanced molecular genetics technology has enabled analysis of complex microbial communities and the study of microbial genomics. Interest has grown in characterizing the microbiome, defined as a collective microbial community and its extensive genome, as a clue to disease mechanisms. "The Human Microbiome Project," sponsored by the NIH Common Fund, was established to characterize the pathology-associated human microbiome in nasal passages, oral cavities, skin, the gastrointestinal tract, and the urogenital compartment. In particular, characterization of urogenital microbiota may elucidate etiologies of complex obstetrical syndromes and factors in fetal development that define risk for pathology in adulthood. This article summarizes recent findings defining the microbiome associated with the female urogenital compartment in child-bearing age women. We also describe our analysis of microbiome samples from the oral, vaginal, and rectal compartments in a cohort of pregnant women. Findings present technical considerations in the characterization of microbial diversity and composition associated with gestational diabetes as a model pregnancy-associated pathology.},
}

@article {pmid23949665,
year = {2013},
author = {Tickle, TL and Segata, N and Waldron, L and Weingart, U and Huttenhower, C},
title = {Two-stage microbial community experimental design.},
journal = {The ISME journal},
volume = {7},
number = {12},
pages = {2330-2339},
pmid = {23949665},
issn = {1751-7370},
support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; },
mesh = {Bias ; Ecology/*methods/standards ; Humans ; Metagenomics ; Microbiological Techniques/*methods/standards ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Research Design/*standards ; },
abstract = {Microbial community samples can be efficiently surveyed in high throughput by sequencing markers such as the 16S ribosomal RNA gene. Often, a collection of samples is then selected for subsequent metagenomic, metabolomic or other follow-up. Two-stage study design has long been used in ecology but has not yet been studied in-depth for high-throughput microbial community investigations. To avoid ad hoc sample selection, we developed and validated several purposive sample selection methods for two-stage studies (that is, biological criteria) targeting differing types of microbial communities. These methods select follow-up samples from large community surveys, with criteria including samples typical of the initially surveyed population, targeting specific microbial clades or rare species, maximizing diversity, representing extreme or deviant communities, or identifying communities distinct or discriminating among environment or host phenotypes. The accuracies of each sampling technique and their influences on the characteristics of the resulting selected microbial community were evaluated using both simulated and experimental data. Specifically, all criteria were able to identify samples whose properties were accurately retained in 318 paired 16S amplicon and whole-community metagenomic (follow-up) samples from the Human Microbiome Project. Some selection criteria resulted in follow-up samples that were strongly non-representative of the original survey population; diversity maximization particularly undersampled community configurations. Only selection of intentionally representative samples minimized differences in the selected sample set from the original microbial survey. An implementation is provided as the microPITA (Microbiomes: Picking Interesting Taxa for Analysis) software for two-stage study design of microbial communities.},
}

Bias
Ecology/*methods/standards
Humans
Metagenomics
Microbiological Techniques/*methods/standards
RNA, Ribosomal, 16S/genetics
Reproducibility of Results
Research Design/*standards

@article {pmid23961316,
year = {2013},
author = {Smith, D and Alverdy, J and An, G and Coleman, M and Garcia-Houchins, S and Green, J and Keegan, K and Kelley, ST and Kirkup, BC and Kociolek, L and Levin, H and Landon, E and Olsiewski, P and Knight, R and Siegel, J and Weber, S and Gilbert, J},
title = {The Hospital Microbiome Project: Meeting Report for the 1st Hospital Microbiome Project Workshop on sampling design and building science measurements, Chicago, USA, June 7th-8th 2012.},
journal = {Standards in genomic sciences},
volume = {8},
number = {1},
pages = {112-117},
pmid = {23961316},
issn = {1944-3277},
support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; },
abstract = {This report details the outcome of the 1st Hospital Microbiome Project workshop held on June 7th-8th, 2012 at the University of Chicago, USA. The workshop was arranged to determine the most appropriate sampling strategy and approach to building science measurement to characterize the development of a microbial community within a new hospital pavilion being built at the University of Chicago Medical Center. The workshop made several recommendations and led to the development of a full proposal to the Alfred P. Sloan Foundation as well as to the creation of the Hospital Microbiome Consortium.},
}