Chatman, L. | Search bioRxiv

bioRxiv2025

Skin microbiome composition and function in the development of atopic diseases during infancy

BackgroundAtopic dermatitis (AD), food sensitization (FS), and food allergy (FA) frequently co-occur in infancy, but the factors driving distinct atopic phenotypes remain unclear. While FLG null mutations are major genetic risk factors for AD, they explain only a fraction of disease heritability, suggesting a potential role for the skin microbiome. ObjectiveTo determine how early-life skin microbiome composition and its interaction with host genetics contribute to distinct atopic phenotypes in infancy. MethodsWe analyzed >1,000 skin swabs from 429 infants in the VITALITY cohort using deep shotgun metagenomic sequencing at 2-3 months (pre-diagnosis) and 12 months (post-diagnosis). Differential abundance, strain-level, and microbial genome-wide association analyses were performed to identify taxonomic and functional features associated with AD, FS, FA, and their co-occurrence, as well as with FLG mutation status. ResultsWithin AD, microbial signatures differed by co-occurring FA or FS. At 12 months, Staphylococcus epidermidis was enriched in infants with AD alone, whereas infants with AD and FA exhibited decreased Staphylococcus hominis and Lactococcus species, along with increased Dermacoccus nishinomiyaensis and Malassezia slooffiae. At 2-3 months, early skin dysbiosis characterized by enrichment of Staphylococcus species was associated with subsequent development of AD with FS or FA, but not AD alone. Among infants with AD, FLG mutation carriers exhibited additional microbial shifts, including reduced Streptococcus species and increased Malassezia slooffiae. Strain-level analyses revealed mother-infant sharing of skin microbial taxa associated with AD, and microbial genome-wide association analyses identified species-specific genes linked to AD severity. ConclusionsInfant atopic phenotypes are associated with distinct, phenotype-specific features of the skin microbiome that emerge both before and after clinical disease onset. By resolving microbial differences within AD according to allergic co-occurrence, host genetics, and early-life timing, this study highlights the infant skin microbiome as a potential target for early risk stratification.

microbiology↗

bioRxiv2023

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 adults in North America and lack representation from infants and individuals from other continents. Here we used ultra-deep shotgun metagenomic sequencing to profile the skin microbiota of 215 infants at age 2-3 months and 12 months who were part of the VITALITY trial in Australia as well as 67 maternally-matched samples. Based on the infant samples, we present the Early-Life Skin Genomes (ELSG) catalog, comprising 9,194 bacterial genomes from 1,029 species, 206 fungal genomes from 13 species, and 39 eukaryotic viral sequences. This genome catalog substantially expands the diversity of species previously known to comprise human skin microbiome and improves the classification rate of sequenced data by 25%. The protein catalog derived from these genomes provides insights into the functional elements such as defense mechanisms that distinguish early-life skin microbiome. We also found evidence for vertical transmission at the microbial community, individual skin bacterial species and strain levels between mothers and infants. Overall, the ELSG catalog uncovers the skin microbiome of a previously underrepresented age group and population and provides a comprehensive view of human skin microbiome diversity, function, and transmission in early life.

genomics↗