| Summary: | The Human Microbiome Project (HMP) [1],[2] is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the “other genome" of microbes carried in and on the human body [3],[4]. Microbial ecologists, realizing that >99% of environmental microbes could not be easily cultured, developed approaches to study microorganisms in situ [5], primarily by sequencing the 16S ribosomal RNA gene (16S) as a phylogenetic and taxonomic marker to identify members of microbial communities [6]. The need to develop corresponding new methods for culture-independent studies [7],[8] in turn precipitated a sea change in the study of microbes and human health, inspiring the new term “metagenomics" [9] both to describe a technological approach—sequencing and analysis of the genes from whole communities rather than from individual genomes—and to emphasize that microbes function within communities rather than as individual species. This shift from a focus on individual organisms to microbial interactions [10] culminated in a National Academy of Science report [11], which outlined challenges and promises for metagenomics as a way of understanding the foundational role of microbial communities both in the environment and in human health.
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