A mixed community of skin microbiome representatives influences cutaneous processes more than individual members

Skin, the largest organ of the human body by weight, hosts a diversity of microorganisms that can influence health. The microbial residents of the skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various skin disorders. Still, much remains to be discovered in terms of the host pathways influenced by skin microorganisms, as well as the higher-level skin properties impacted through these microbe-host interactions. Towards this direction, recent efforts using mouse models point to pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community. However, there is a need to quantify the roles of microorganisms at both the individual and community-level in healthy human skin. In this study, we utilize human skin equivalents to study the effects of individual taxa and a microbial community in a precisely controlled context. Through transcriptomics analysis, we identify key genes and pathways influenced by skin microbes, and we also characterize higher-level impacts on skin processes and properties through histological analyses. The presence of a microbiome on a 3D skin tissue model led to significantly altered patterns of gene expression, influencing genes involved in the regulation of apoptosis, proliferation, and the extracellular matrix (among others). Moreover, microbiome treatment influenced the thickness of the epidermal layer, reduced the number of actively proliferating cells, and increased filaggrin expression. Many of these findings were evident upon treatment with the mixed community, but either not detected or less pronounced in treatments by single microorganisms, underscoring the impact that a diverse skin microbiome has on the host. This work contributes to the understanding of how microbiome constituents individually and collectively influence human skin processes and properties. The results show that, while it is important to understand the effect of individual microbes on the host, a full community of microbes has unique and pronounced effects on the skin. Thus, in its impacts on the host, the skin microbiome is more than the sum of its parts.

Micrococcus luteus, Streptococcus luteciae, Staphylococcus epidermidis, Streptococcus luteciae, Roseomonas mucosa, Acinetobacter lwoffi, Corynebacterium sp., Streptococcus, Staphylococcus, Paenibacillus, Micrococcus, Bacillus sp., KI67, filaggrin, loricrin, Skin microbiome, Skin proliferation, Host-microbiome interaction, RNA sequencing, Cutaneous transcriptome, epidermal thickness, LCN2, beta-defensin 4A (DEFB4A), S100-A7A, gene expression

Micrococcus luteus, Streptococcus luteciae, Staphylococcus epidermidis, Streptococcus luteciae, Roseomonas mucosa, Acinetobacter lwoffi, Corynebacterium sp., Streptococcus, Staphylococcus, Paenibacillus, Micrococcus, Bacillus sp.