A genome catalog of the early-life human skin microbiome

Metagenome-assembled genomes have greatly expanded the reference genomes for skin microbiome. However, the current reference genomes are largely based on samples from children and adults in North America and lack representation from infants and individuals from other continents. Here we used ultra-deep shotgun metagenomics sequencing to profile the skin microbiota of over 500 skin swabs collected longitudinally at age 2 months and 12 months from 217 infants who were part of a vitamin D supplementation food allergy prevention trial in Australia, Oceania. Each sample yielded about 10 million non-human reads or 1 billion base pairs on average. To build metagenome-assembled genomes, we used MEGAHIT for assembly and a combination of MetaBAT, MaxBin, and CONCOCT for binning. Prokaryotic genomes were further refined with metaWRAP and then checked for chimerism with GUNC, and eukaryotic genomes were checked for quality with EukCC. We present the Early-Life Skin Genomes (ELSG) catalog, comprising 9,096 nonredundant prokaryotic and 227 eukaryotic genomes with more than 50% completeness and less than 10% contamination. This genome catalog substantially expanded the diversity of species known to comprise the skin microbiome and improved the classification rate of sequenced data by 25% over the standard Kraken 2 database. The protein catalog derived from these genomes provided insights into the functional elements that distinguish early-life skin microbiome. For example, the proteins specific to the ELSG were enriched for functions related to defense mechanisms. By comparing microbial profiles and genomes from 67 mother-infant pairs, we discovered mother-infant transmission of skin microbiome for 7 different species, including Cutibacterium acnes, Rothia mucilaginosa, and Micrococcus luteus. We also found temporal persistence of microbiome within the same infant by analyzing longitudinal samples at two different times. Overall, the ELSG uncovers the skin microbiome of a previously underrepresented age group and population and provides a comprehensive view of skin microbiome diversity, function, and transmission in early life.