Impact of host genetic variation and environmental influences on the cutaneous microbiome composition
General Genetics and Functional Genome Biology
Epidemiology and Medical Biometry/Statistics
Final Report Abstract
The human skin offers diverse ecosystems for microbial symbionts. However, the intrinsic and extrinsic factors shaping the skin–microbiome are still insufficiently characterized. We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two large cross-sectional German populations, KORA FF4 (n = 353) and PopGen (n = 294), totalling 1794 skin samples. The V1–V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. A meta-analyses of genome-wide association studies (GWAS) identified 30 genome-wide significant loci harbouring candidate genes involved in innate immune signalling, environmental sensing, apoptosis, cell differentiation and proliferation. Mendelian randomization (MR) analysis confirmed the influence of staphylococci on eczema/dermatitis and suggested modulating effects of the microbiota on other skin diseases. Finally, putative effects of the common skin bacterium Staphylococcus epidermidis on the expression of identified candidate genes of interest in keratinocytes were revealed. With our study we expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria and hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a larger extent compared with a single skin physiological feature, lifestyle and environmental exposure. Our GWAS results confirm the close interaction of host genetics and associated microbiomes and point to the skin microbiota as a target for disease prevention and management, with potential for the development of personalized treatments for non-infectious, inflammatory skin conditions.
Publications
- Host traits, lifestyle and environment are associated with the human skin bacteria. Br J Dermatol, 185(3):573-584, 2021
Moitinho-Silva L, Boraczynski N, Emmert H, Baurecht H, Szymczak S, Schulz H, Haller D, Linseisen J, Gieger C, Peters A, Tittmann L, Lieb W, Bang C, Franke A, Rodriguez E, Weidinger S
(See online at https://doi.org/10.1111/bjd.20072)
