Evolving approaches to profiling the microbiome in skin disease

Abstract

Despite its harsh and dry environment, human skin is home to diverse microbes, including bacteria, fungi, viruses, and microscopic mites. These microbes form communities that may exist at the skin surface, deeper skin layers, and within microhabitats such as the hair follicle and sweat glands, allowing complex interactions with the host immune system. Imbalances in the skin microbiome, known as dysbiosis, have been linked to various inflammatory skin disorders, including atopic dermatitis, acne, and psoriasis. The roles of abundant commensal bacteria belonging to Staphylococcus and Cutibacterium taxa and the fungi Malassezia, where particular species or strains can benefit the host or cause disease, are increasingly appreciated in skin disorders. Furthermore, recent research suggests that the interactions between microorganisms and the host's immune system on the skin can have distant and systemic effects on the body, such as on the gut and brain, known as the "skin-gut" or "skin-brain" axes. Studies on the microbiome in skin disease have typically relied on 16S rRNA gene sequencing methods, which cannot provide accurate information about species or strains of microorganisms on the skin. However, advancing technologies, including metagenomics and other functional 'omic' approaches, have great potential to provide more comprehensive and detailed information about the skin microbiome in health and disease. Additionally, inter-species and multi-kingdom interactions can cause cascading shifts towards dysbiosis and are crucial but yet-to-be-explored aspects of many skin disorders. Better understanding these complex dynamics will require meta-omic studies complemented with experiments and clinical trials to confirm function. Evolving how we profile the skin microbiome alongside technological advances is essential to exploring such relationships. This review presents the current and emerging methods and their findings for profiling skin microbes to advance our understanding of the microbiome in skin disease.

Keywords: acne (acne vulgaris); atopic dermatitis (AD); genomics; metagenomics; microbiome and dysbiosis; next-generation sequencing; psoriasis.

Figure 1

Timeline of selected microbiome toolbox milestones and skin microbiome profiling highlights.

Figure 2

Healthy human skin is host to a diverse range of microbes across multiple skin layers and microenvironments. Skin bacteria, many of which belong to the Cutibacterium, Staphylococcus, Corynebacterium, and Streptococcus genera, are resident members of the skin microbiome. The skin eukaryome commonly includes fungi and microscopic mites belonging to the Malassezia and Demodex genera, respectively. Viruses, most notably including Staphylococcus phages, Cutibacterium phages, human Papillomaviruses, and human Polyomaviruses, are among the dominant members of the skin virome. Archaea (not pictured) has also been identified on the skin microbiome, though likely with a minor or transient presence. Microbial diversity and biomass are typically higher at the skin surface. However, human skin is a three-dimensional space, and microbes form communities that live at the skin surface, deeper skin layers, and within microhabitats such as the hair follicle and sweat glands, allowing complex inter-species relationships and interactions with the host immune system.