The Human Microbiome: at the interface of health and disease
Nat Rev Genet. Author manuscript; available in PMC 2012 October 1.
Published in final edited form as:
PMCID: PMC3418802
NIHMSID: NIHMS388822
The Human Microbiome: at the interface of health and disease
The Human Microbiome: at the interface of health and disease
The publisher's final edited version of this article is available at Nat Rev Genet
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Until recently, the properties of the microbiota of humans (formerly called ‘the normal flora’) were largely a black box. Cultivation in vitro, which has been the cornerstone of microbiology since the 19thcentury, cannot be applied to many of the most densely populated microbial communities1. However, DNA-based analyses have expanded our horizon, by generating enormous new data sets that can be mined for information on the composition and functional properties of vastly greater numbers of microbial communities. For example, the Human Microbiome Project (HMP) by the NIH has produced a 2.3 terabyte 16S rRNA metagenomic dataset of over 35 billion reads taken from 690 samples from 300 U.S. subjects, across 15 body sites. Large-scale endeavors (e.g. the HMP2 and also the European project, Metahit3) provide a preliminary understanding of the biology and medical significance of the humanmicrobiome and its collective genes (the metagenome).
The aim of these projects, particularly the HMP, is to characterize the compositional range of the ‘normal’ microbiome of healthy individuals. Important questions concerning the commonalities and differences between healthy individuals in both microbial taxa and functional pathways are being addressed. The presence of major clustering patterns at body sites such as the vagina4 and the gastrointestinal tract5 provide new ways to classify individuals, and possibly, their disease risks. Substantial progress has been made in developing the tools for inquiry, and defining the overarching concepts that advance the field. However, the subject is vast, and the implications for human health and disease are wide-ranging. The study of humans and model animal systems with strong phenotypes is essential for making progress in this field of applied genetics. Although a focus on bacteria is important, inquiries aimed at archaea, viruses, and retroviruses, is also needed.
The purpose of this review is to develop the theoretical basis for investigating how microbiome composition and function affect human health. We provide examples of applying this knowledge to better understand human health, and discuss how microbiome changes could alter host–microbiome interactions to mitigate disease. We also consider the next steps in the development of this field, particularly on the need to focus on the inheritance of the microbiome, and on its involvement in modulating complex traits.
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