Both the Metagenomics of the Human Intestinal Tract (MetaHIT) project, supported by the European Comission under the 7th Framework program, and the Human Microbiome Project (HMP), supported by the National Institutes of Health (NIH), are the largest studies to date that have characterized the microbiomes of healthy human subjects at different body sites using 16S and shotgun metagenomic sequencing.
A new study, led by Dr. Curtis Huttenhower from the Biostatistics Department at Harvard T. H. Chan School of Public Health and the Broad Institute in Massachusetts (USA), has provided an updated body-wide metagenomics profile of the human microbiome.
Based on biospecimens previously collected during the first wave of the HMP, the researchers analysed, using whole-metagenome sequencing and updated profiling and assembly methods, 1,631 new samples from the HMP cohort (for a total of 2,355). 6 major body sites were targeted -anterior nares, buccal mucosa, supragingival plaque, tongue dorsum, stool and posterior fornix- at 3 time points in 265 individuals.
A new metagenomics strain identification approach -which identified the dominant strain of each sufficiently abundant species in a metagenome- revealed temporally stable subspecies population structures for several species, with differences over time being lower than differences between people. The time-varying component reported by differences over time in the human gut microbiome is in agreement with the previous HMP data. Specifically, some species were unique to individuals and others were associated with particular body sites. Besides this, strain identification also quantified species with a strain diversity under-represented in isolate genomes.
Co-occurrence patterns between bacterial communities and several archaea, eukaryotes, and viruses were also identified by new taxonomic profiling. These results depict a more comprehensive picture of how commensal microorganisms in the human microbiome interact, therefore driving forward a better characterization of gut microbiota research.
Through new functional profiling methods, pathways required for microbial colonization of the human body were identified and classified into universal, human-enriched, and body site-enriched subsets. On the whole, 28 metabolic pathways were core at all 6 body sites studied. Besides this, 17 additional pathways were core in multiple body areas, whereas 21 pathways were considerably more abundant in the oral body areas compared to other body areas. For instance, nitrate reduction was enriched in the oral cavity and degradation of mannan -a kind of plant polysaccharide- was enriched in the gut. These data indicate microbial community adaptation to specific human body sites, as well as essential metabolic processes broadly distributed in the human body.
Microbial composition and its functional variation were characterized over time. Bacteroidetes species in the gut showed primarily inter-individual variation, whereas Firmicutes species varied most temporally within individuals. Based on these results, the authors believe that the Bacteroidetes/Firmicutes ratio should not be used anymore as a defining attribute of an individual’s gut microbiome. Species abundances in the oral and skin microbiomes exhibited greater time-varying dynamics, which makes them less reliable to distinguish one person from another. Altogether these data show that commensal microbial species show different dynamics between body sites and are influenced by both intra- and inter-individual variability.
In conclusion, this study has shed light on microbiome stability and dynamics over time in multiple body sites. It provides a large data resource for other microbiome scientists to use in their upcoming research. Further follow-up studies are needed with large numbers of samples from different populations, taking into account more time points and assessing the effects of controlled perturbations rather than using a descriptive approach.
Lloyd-Price J, Mahurkar A, Rahnavard G, et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature. 2017. doi: 10.1038/nature23889.