Comparative Metagenomics Revealed Commonly Enriched Gene Sets in Human Gut Microbiomes

TLDR

The human intestine hosts a diverse, largely uncharacterized microbial community that profoundly influences physiology. The study aims to identify genomic features common to all human gut microbiomes and those that vary among them. This was achieved by performing a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. The analysis revealed that infant microbiomes are simpler with high inter-individual variation, while adult and weaned child microbiomes are more complex yet functionally uniform; 237 gene families were commonly enriched in adult-type and 136 in infant-type microbiomes with minimal overlap, and 647 orphan gene families were uniquely present in human gut microbiomes, including a conjugative transposon family highly amplified, indicating the intestine as a hotspot for horizontal gene transfer.

Abstract

Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a 'hot spot' for horizontal gene transfer between microbes.