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.
Highlights
The human body is home to an enormous number and diversity of microbes
We observed a substantial number of chimeras within the Human Microbiome Project (HMP) dataset, which were removed with the program UCHIME (Document S1 and Figures S1, S2, S3) [23], resulting in 773 V1–V3 and 695 V3–V5 non-chimeric HMP operational taxonomic units (OTUs)
We assert that a modest sequencing effort combined with existing databases will result in genome sequences being available for a large majority of the most common microbial taxa present in the human microbiome
Summary
The human body is home to an enormous number and diversity of microbes. These microbes, the human microbiome, are increasingly thought to be required for normal human development, physiology, immunity, and nutrition [1,2,3]. The mission of the Human Microbiome Project (HMP) is to understand the role of human-associated microbial communities in health and disease As part of this mission, the HMP seeks to generate a comprehensive reference collection of microbial genomes that represent the ‘‘healthy’’ human microbiome [12,13,14]. Through the efforts of the HMP and other sequencing projects, nearly 5,000 bacterial strains have been isolated from the human body, grown in culture and submitted for whole genome sequencing While these organisms represent a wide range of taxonomic groups and origins of isolation, studies suggest that many microbes, including those that inhabit humans, have not been cultured and, elude conventional methods for DNA preparation and sequencing [15,16].
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