The human microbiome: our second genome.

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Abstract

The human genome has been referred to as the blueprint of human biology. In this review we consider an essential but largely ignored overlay to that blueprint, the human microbiome, which is composed of those microbes that live in and on our bodies. The human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions. Characterization and analysis of the human microbiome have been greatly catalyzed by advances in genomic technologies. We discuss how these technologies have shaped this emerging field of study and advanced our understanding of the human microbiome. We also identify future challenges, many of which are common to human genetic studies, and predict that in the future, analyzing genetic variation and risk of human disease will sometimes necessitate the integration of human and microbial genomic data sets.

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Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors.

Andrew Benson, Scott Kelly, Ryan M Legge … (2010)

In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases.

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Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome.

David T. Pride, Julia Salzman, Matthew Haynes … (2012)

Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host-virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.

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The Human Microbiome Project in 2011 and beyond.

Lita M. Proctor (2011)

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. Copyright © 2011 Elsevier Inc. All rights reserved.

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Journal

Journal ID (iso-abbrev): Annu Rev Genomics Hum Genet

Title: Annual review of genomics and human genetics

Publisher: Annual Reviews

ISSN (Electronic): 1545-293X

ISSN (Print): 1527-8204

Publication date (Electronic): 2012

Volume: 13

Affiliations

[1 ] Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Article

Mid ID: NIHMS424103

DOI: 10.1146/annurev-genom-090711-163814

PMC ID: 3518434

PubMed ID: 22703178

SO-VID: 02f46a14-67a9-4e1d-9114-f3bc38242d97

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The human microbiome: our second genome.

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Abstract

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Tick microbiome

Most cited references 3

Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors.

Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome.

The Human Microbiome Project in 2011 and beyond.

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