Obtaining a close characterization of human microbial diversity and abundance remains a challenge for the researchers of today. In the past, microbial composition was studied using culture-based methods that underestimated diversity, as only between 20% and 50% members are culturable. Over the past decade, our understanding of the composition and diversity of the gut microbiota has advanced through culture-independent methods based on the characterization of 16S ribosomal ribonucleic acid (rRNA) genes and, most importantly, due to next generation sequencing approaches. These techniques provide information on the functional and metabolic potential of the human microbiota. However, the human body harbors a huge number of microbial species that have yet to be characterized in international populations.
A new study, led by Dr. Nicola Segata from the Laboratory of Computational Metagenomics at the University of Trento (Italy), has now provided the largest ever catalog of human-associated microbes across worldwide populations. The researchers used a large-scale approach, integrating computational genomics (the study of the human microbiome by analyzing its genetic information), microbiology and big data to characterize and catalog bacterial and archaeal genomes from oral cavity, skin, vagina and stool samples. Participants were individuals of all ages living in 32 different countries, with both Westernized and non-Westernized lifestyles, and they included a newly added cohort from Madagascar.
The metagenomic assembly of 9,428 human microbiome samples from across all body sites allowed for the reconstruction of 154,723 new microbial genomes from 4,930 species. A large fraction (77%) were previously unexplored and uncharacterized, therefore increasing the number of gut microorganism genomes that are mappable, or which can be prioritized for analysis. Specifically, non-Westernized gut microbiomes showed increased metagenomic read mappability compared with their Westernized counterparts, while gut and oral cavity metagenomes had the highest mappability, followed by those of the vagina and finally the skin.
By reconstructing more than 1,800 genomes, the researchers found that among previously unknown species, the seventh most prevalent human-associated microbe in the worldwide population was “Candidatus Cibiobacter qucibialis”. This species was phylogenetically placed between Faecalibacterium and Ruminococcus.
The vast majority of genomes from Westernized populations clustered together, whereas genomes from the non-Westernized populations grouped separately. Interestingly, many of the characterized microbes tended to be more prevalent in communities with non-Western lifestyles. For example, the gut microbiomes of rural non-Westernized populations showed a strong presence of Succinatimonas sp., suggesting specialization to host lifestyles, in particular in relation to degrading the plant-sugar xylose. In contrast, Bacteroides species were the strongest bacteria associated with a Westernized lifestyle.
Some differences were also found at a functional level. Genes involved in antibiotic biosynthesis and genes for tryptophan metabolism were both expressed differently in Westernized vs. non-Westernized populations, reflecting the broad ways in which the gut microbiome adapts to the environment of different human populations. In fact, the researchers described these differences as an indirect consequence of the complex industrialization processes that have taken place in Westernized populations.
On the whole, this new computational metagenomic study has expanded the number and diversity of bacteria in the human body across both Westernized and non-Westernized international populations. These findings expand our current knowledge of the abundance and diversity of the human microbiome and support continued research into the as yet unexplored diversity of a large part of the human microbiome.
Pasolli E, Asnicar F, Manara S, et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomics spanning age, geography, and lifestyle. Cell. 2019. doi: 10.1016/j.cell.2019.01.001.