The global prevalence of allergic diseases has increased dramatically, paralleling the rapid urbanization and modernization that followed World War II. This shift toward urban living has led to a dramatic reduction in human exposure to biodiverse and natural environments. According to the biodiversity hypothesis, this decline in exposure results in a deprivation of the human microbiome—the community of microorganisms living in the human body, which is crucial for immune modulation and overall health. Consequently, a disturbed immune regulation and increased risk of inflammatory disorders, such as allergies, are observed. The skin microbiome is strategically located at the interface of the body and the environment, receiving continuous input from the external world, making it a proxy for environmental microbial exposure and an important factor in modulating allergy risk.
The study focuses on the Karelian region, which spans the Finnish-Russian border, offering a unique contrast where geographically similar populations experience vastly different environmental exposures and allergy prevalence: Finnish Karelia is urbanized with high allergy rates, while Russian Karelia is rural with low allergy rates. Although previous amplicon sequencing studies demonstrated genus-level differences in skin microbiota between the populations, they failed to distinguish differences between allergen-sensitized and non-sensitized individuals. Therefore, researchers employed whole metagenome shotgun (WMS) sequencing to provide high-resolution species- and strain-level classification of bacteria, archaea, fungi, and DNA viruses, aiming to better understand the interplay among the environment, the skin microbiome, and IgE-mediated allergic sensitization.
Methods
A subgroup of 112 adolescents (ages 15–20), consisting of 60 Finnish and 52 Russian participants, was selected to facilitate comparison between allergen-sensitized (categorized by serum IgE levels into Non-Sensitized, Intermediate, and Highly Sensitized groups) and non-sensitized individuals across the contrasting environments. DNA was extracted from volar forearm skin swab samples. Whole metagenome shotgun sequencing was performed on the DNA. Taxonomic and strain-level classification utilized MetaPhlAn and StrainPhlAn, and statistical analyses, including PERMANOVA and distance-based redundancy analysis (dbRDA), were used to associate microbial compositions with allergic sensitization and environmental exposure. Network analysis was also applied to visualize species co-occurrence relationships.
Key Findings
• In Finnish Karelia (the urbanized region), the skin microbiome composition was associated with IgE-mediated allergen sensitization status, particularly levels of birch-specific sIgE.
• In Russian Karelia (the rural region), the skin microbiome composition was associated primarily with environmental exposure factors, such as dog and cat ownership and interaction frequency, and did not significantly differentiate between allergic sensitization categories.
• Finnish highly sensitized participants (HS) displayed a lower abundance of Cutibacterium acnes and total Malassezia species (including M. globosa and M. sympodialis) compared to non-sensitized (NS) participants.
• The microbial co-occurrence network was weaker and less interconnected in Finnish highly sensitized participants compared with non-sensitized participants.
• Analysis of genomic variation showed that Malassezia restricta strain-level differences were related to allergic sensitization categories (NS, SI, HS) in both Finnish and Russian participants, suggesting a functional genomic association with allergy independent of geographic location.
• The skin microbiomes of Russian participants were characterized by greater species diversity and richness and a higher abundance of species typical of soil and aquatic environments, such as Acinetobacter johnsonii and Acinetobacter lwoffii.
The research provides novel species- and strain-level characterization of the skin microbiome, extending previous findings limited to the genus level. By utilizing WMS sequencing, the study demonstrated that the skin microbiome composition is significantly linked with IgE-mediated sensitization in the urbanized Finnish population. The discovery of the association between Malassezia restricta strain phylogeny and allergic sensitization in both geographic groups highlights the novelty of inspecting microbial genomes, suggesting that the role of the microbiome in allergy may be strain-specific and functional, rather than merely compositional.
The future implication of this work is significant, promoting further mechanistic research on the role of the skin microbiome in health, especially in the context of urban lifestyles and reduced exposure to nature. The findings strongly suggest that the interplay between the skin microbiome and allergic sensitization should be investigated through microbial genomes and functionality to fully elucidate the complex mechanisms involved. Ultimately, improved knowledge in this area can support the planning of urban environments designed to preserve natural biodiversity, which may offer health benefits for the human population.
Link to the study: Shotgun metagenomics reveals distinct skin microbial species in allergen-sensitized individuals | Microbiology Society
