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Expanded Human Microbiome Project Examines Dynamics, Functions of Microbial Communities

NEW YORK (GenomeWeb) – Researchers have characterized more than 1,600 additional samples in an effort to understand the human microbiome.

The study is an extension of the second phase of the Human Microbiome Project. The first phase of the project was launched in 2007 by the US National Institutes of Health to characterize the role of the microbiome in health and disease as well as generate reference genomes for such microbes. In more than a dozen publications in 2012, HMP researchers reported on the microbial makeup of samples collected from hundreds of people at more than a dozen body sites.

The second phase of the HMP was funded the following year with the aim of focusing on the biochemical activities of the human microbiome.

In a paper appearing today in Nature, researchers led by Curtis Huttenhower of the Broad Institute and Harvard T.H. Chan School of Public Health reported on the whole-metagenome sequencing of 1,631 new samples from the HMP cohort.

"This study has given us the most detailed information to date about exactly which microbes and molecular processes help to maintain health in the human microbiome," said Huttenhower in a statement.

He and his colleagues analyzed new samples from 265 individuals, collected from at least six body sites and at multiple points in time. This new set encompassed 2,103 unique metagenomes and 252 technical replicates. This extended the HMP set to 2,355 metagenomes.

Using the computational tool StrainPhlAn, the researchers examined the stability and diversity of their set of metagenomes. Strain profiles were consistent over time, they reported. The differences they observed in samples collected from the same person at different time points were smaller than the differences between samples collected from different people.

Certain subspecies of microbial strains, though, tended to crop up at specific body sites, the researchers found. At the extreme, they noted that distinct subspecies clades of Haemophilus parainfluenzae were found at various sites in the mouth — in tooth plaque, the inside lining of the cheek, and the top of the tongue.

Other microbes tended to appear together. Methanobrevibacter smithii was present alongside gut-dwelling Clostridiales like members of the Ruminococcus, Coprococcus, Eubacterium, and Dorea genera.

Because microbial samples were collected at multiple points in time, Huttenhower and his colleagues could begin to tease out the dynamics of the various body site communities. Within the gut microbiome, they noted that the Firmicutes were dynamic over time within individuals, though Bacteroides varied more between individuals. Meanwhile, some species, like Rothia dentocariosa, followed similar dynamic patterns at the various body sites where they were located.

Broadly, though, they found that species-level changes largely reflected community-level dynamics in the same cohort.

The researchers also assessed the 'coreness' of certain molecular functions of the microbes. They deemed a functional pathway to be 'core' to a certain body site if it was present among three-quarters of the people sampled. In that way, they identified 258 pathways that were core to at least one body site as well as others that were 'multicore' or 'supercore' pathways and present in many or all body sites examined.

Core pathways tended to be broadly distributed among taxonomic groups and include essential metabolic pathways like coenzyme A and adenosine nucleotide biosynthesis. At the same time, though, some core pathways like nitrate reduction and mannan degradation are limited to certain body sites and may reflect community adaptation to that site.

Even with this onslaught of data, Huttenhower and his colleagues noted that much of the human microbiome remains to be characterized.

"These communities of organisms are tremendously complex. In one sense, this study is a great advancement for the research community," said author Anup Mahurkar from the University of Maryland School of Medicine in a statement. "On the other hand, it still just moves the needle. There will always be more we can learn."

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