Abstract

BackgroundCharacterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. Previous studies mainly focused on a single body habitat from a limited set of subjects. Here, we analyzed one of the largest microbiome datasets to date and generated a biogeographical map that annotates the biodiversity, spatial relationships, and temporal stability of 22 habitats from 279 healthy humans.ResultsWe identified 929 genera from more than 24 million 16S rRNA gene sequences of 22 habitats, and we provide a baseline of inter-subject variation for healthy adults. The oral habitat has the most stable microbiota with the highest alpha diversity, while the skin and vaginal microbiota are less stable and show lower alpha diversity. The level of biodiversity in one habitat is independent of the biodiversity of other habitats in the same individual. The abundances of a given genus at a body site in which it dominates do not correlate with the abundances at body sites where it is not dominant. Additionally, we observed the human microbiota exhibit both cosmopolitan and endemic features. Finally, comparing datasets of different projects revealed a project-based clustering pattern, emphasizing the significance of standardization of metagenomic studies.ConclusionsThe data presented here extend the definition of the human microbiome by providing a more complete and accurate picture of human microbiome biogeography, addressing questions best answered by a large dataset of subjects and body sites that are deeply sampled by sequencing.

Highlights

  • Characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases

  • We addressed the following aspects of human microbial biogeography in the context of a large cohort and deep sequencing: how many organisms inhabit the human body; is the biodiversity of one habitat influenced by other habitats; is the presence or abundance of the organism in one habitat affected by other habitats; what is the bacterial distribution pattern in a habitat; what is the degree of inter-personal variation and temporal variation in different habitats; are the Human Microbiome Project (HMP) data comparable with the prior human microbiome studies

  • Overview of the datasets Sample collection, DNA extraction, sequencing, as well as data processing followed the manual of procedures of the HMP consortium [24]

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Summary

Introduction

Characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. The NIH launched the Human Microbiome Project (HMP) [23], aiming to more fully characterize the human microbiota and address its role in health and disease This project enrolled 300 healthy, young adults, collected samples from 15 (male) or 18 (female) habitats in the body, and produced datasets of both 16S rRNA gene and whole genome shotgun (WGS) sequences [24]. The RDP taxonomic approach used in this study possesses easy interpretability and better sequence error tolerance It provides confident taxonomic assignment at the genus and other higher taxonomic levels. The phylogenetic approach dependent on the tree construction provides phylogeny of the bacterial community, but it inevitably bears the intrinsic problems of tree construction using short reads Each of these methods has its pros and cons, and they are complementary to each other. They provide important insight into the bacterial community structure [30]

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