A compendium of 32,277 metagenome-assembled genomes and over 80 million genes from the early-life human gut microbiome

Given the specificity of early-life human gut microbiome regarding the microbial composition and functions, building a set of high-quality reference genomes from early life is desirable for a good microbial characterization, and discovering interactions between early-life gut microbiome and health.

The gut microbiome is a critical determinant to maintain the human health, and any disturbances of the balance might be related to various diseases throughout the course of life. Increasing evidences have illustrated that these long-term negative consequences stem from the aberrant early-life gut microbiome. Therefore, a good characterization of the early-life gut microbiome is essential to illustrate the correlation between the gut microbiome and health. It is well-known that the early-life gut microbiome is uniquely characterized with taxonomic and functional properties and dynamic profiles until reaching 2-3 years old, being different from adults, such as the microbial compacities to degrade and utilize the human milk oligosaccharides. Therefore, a set of high-quality reference genomes of this particular life period is mandatory for the good characterization of the myriad of gut microbiota and microbial functions.

In order to fill this gap, we specifically analyzed over 6,000 fecal metagenomes from children under the first three years of life, and generated a set of 32,277 metagenome-assembled genomes (MAGs) clustered into 2,172 species-level clusters together with 86,678,654 genes representing 4,036,936 gene clusters, forming the Early-Life Gut Genomes (ELGG) and Proteins (ELGP) catalogs, respectively. With these comprehensive sequence collections, we characterized the taxonomic and functional profile of the early-life gut microbiome at the genome level and interrogated the genomic variations present in the gut microbiome of children associated with various clinical factors. The ELGG substantially expanded the phylogenetic diversity by 38% over the isolate microbial genomes, and the genomic landscape of the early-life gut microbiome by increasing recruitment of metagenomic reads over 80%.

Overall, the newly reconstructed genomes provide a novel insight for the human early-life gut microbiome and reveal a high resolution in the taxonomic, functional and genomic diversity of early life. The establishment of ELGG and ELGP catalogs will substantially offer ability to understand the development and mechanisms of disturbances of the early-life gut microbiome. The ELGG and ELGP references will facilitate studies to understand the development and mechanisms of alteration of the human gut microbiome in early life.

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