Genomic blueprint of the human gut microbiota — via multiple co-assembled metagenomes

The importance of our intestinal bacteria (“the gut microbiome“) has often been discussed in these GEITP pages. The extent to which our microbomes contribute to our inter-individual health, disease risk, and even response to drugs and environmental toxicants is a research field that is still in its infancy. Many microbial reference genomes can be essential resources for understanding functional roles of specific organisms in the microbiome, but the genomes of at least 40–50% of human gut species have not yet been determined.


The attached articles represent a new experimental approach: “metagenome binning” (a computational approach that can be used to obtain genomes directly from samples of MANY species without individual bacterial isolation or culturing). Sequencing reads are first assembled into contigs (sets of overlapping DNA segments that together represent a consensus region of DNA), which are then binned into metagenome-assembled genomes (MAGs) on the basis of nucleotide frequency, abundance, and/or co-variation of abundance across groups of samples; this process can be performed either for individual metagenomes or multiple co-assembled metagenomes. MAGs are subsequently evaluated for various indicators of genome quality, including estimated completeness and contamination, presence of marker genes, and overall contiguity. With advances in sequencing technology and computational methods, MAGs have now been recovered from many environments including the global ocean, cow rumen, aquifer systems, etc. These uncultured genomes have expanded the Tree of Life by revealing novel lineages in diverse environments.


Authors [see attached first article] identified 1,952 uncultured candidate bacterial species by reconstructing 92,143 MAGs from 11,850 human gut microbiomes. These data substantially expand the known species repertoire of the collective human gut microbiota, with a ~280% increase in phylogenetic diversity. Although the newly identified species are less prevalent in well-studied populations compared to reference isolate genomes they improve classification of understudied microbiomes from humans of African and South American ancestry by more than 200%. These candidate species encode hundreds of newly identified biosynthetic gene clusters and possess distinctive functional capacities that might explain their elusive nature.


Authors [see attached second article] reconstructed 60,664 draft prokaryotic (bacterial, viral) genomes from 3,810 fecal metagenomes, from geographically and phenotypically diverse humans; these genomes provide reference points for 2,058 newly identified species-level Operational Taxonomic Units (OTUs), which represents a ~50% increase over previously known phylogenetic diversity of sequenced gut bacteria. On average, the newly identified OTUs comprise 33% of richness and 28% of species abundance per individual; they are more predominant in humans from rural populations. Authors state that their analysis revealed that uncultured gut species have undergone genome reduction that has resulted in the loss of certain biosynthetic pathways which may offer clues for improving cultivation strategies in the future. These MAGs of clinical gut-microbiome studies have identified numerous disease associations for the newly identified OTUs, which have the potential to improve predictive models.






Nature   25 Apr 2o19; 568: 499-504 & 505-510

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