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

Area of Science:

• Microbiome research
• Pediatric allergy
• Dermatology

Background:

• Atopic dermatitis (AD), food sensitization (FS), and food allergy (FA) often co-occur in infants.
• Filaggrin (FLG) mutations are key genetic risk factors for AD, but do not fully explain disease heritability.
• The infant skin microbiome may play a significant role in AD development and distinct atopic phenotypes.

Purpose of the Study:

• To investigate how early-life skin microbiome composition and host genetics interact to influence distinct infant atopic phenotypes.
• To identify specific microbial signatures associated with AD, FS, FA, and their co-occurrence.
• To explore the role of the skin microbiome in relation to FLG mutation status in infants.

Main Methods:

• Deep shotgun metagenomic sequencing of over 1,000 skin swabs from 429 infants at 2-3 and 12 months of age.
• Differential abundance, strain-level, and microbial genome-wide association analyses were performed.
• Analysis included taxonomic and functional features related to AD, FS, FA, and FLG mutation status.

Main Results:

• Distinct microbial signatures were observed within AD, varying by co-occurring FA or FS.
• Early skin dysbiosis, marked by Staphylococcus enrichment at 2-3 months, predicted subsequent AD with FS or FA.
• FLG mutation carriers with AD showed additional microbial shifts, including reduced Streptococcus and increased Malassezia slooffiae.

Conclusions:

• Infant atopic phenotypes are associated with specific skin microbiome features appearing before and after disease onset.
• Resolving microbial differences within AD based on allergic co-occurrence, genetics, and timing is crucial.
• The infant skin microbiome represents a promising target for early risk stratification of atopic diseases.