The Skin Microbiome: Current Techniques, Challenges, and Future Directions

Abstract

Skin acts as a barrier that promotes the colonization of bacteria, fungi, archaea, and viruses whose membership and function may differ depending on the various specialized niches or micro-environments of the skin. The group of microorganisms inhabiting the skin, also known as the skin microbiome, offers protection against pathogens while actively interacting with the host's immune system. Some members of the skin microbiome can also act as opportunistic pathogens. The skin microbiome is influenced by factors such as skin site, birth mode, genetics, environment, skin products, and skin conditions. The association(s) of the skin microbiome with health and disease has (have) been identified and characterized via culture-dependent and culture-independent methods. Culture-independent methods (such as high-throughput sequencing), in particular, have expanded our understanding of the skin microbiome's role in maintaining health or promoting disease. However, the intrinsic challenges associated with the low microbial biomass and high host content of skin microbiome samples have hindered advancements in the field. In addition, the limitations of current collection and extraction methods and biases derived from sample preparation and analysis have significantly influenced the results and conclusions of many skin microbiome studies. Therefore, the present review discusses the technical challenges associated with the collection and processing of skin microbiome samples, the advantages and disadvantages of current sequencing approaches, and potential future areas of focus for the field.

Keywords: culture-independent methods; metatranscriptomics; shotgun metagenomics; skin microbiome.

Figure 1

Overview of a standard skin microbiome analysis pipeline. A skin microbiome analysis pipeline includes study design, sample collection, processing, sequencing, and bioinformatic analysis. Some steps within sample processing and bioinformatics may be specific to certain sequencing approaches (e.g., amplicon target within sample processing is specific for targeted or amplicon sequencing and host removal may be specific for untargeted sequencing). The figure also shows several of the steps that may add biases to a skin microbiome pipeline (discussed in this review); these were also previously described for microbiome studies and applied in skin microbiome research [24]. PCR: polymerase chain reaction.

Figure 2

Highlights of some of the potential future directions and applications of skin microbiome research. These include, but are not limited to, deciphering multi-kingdom interactions, developing therapeutics, forensic applications, and integrating various ‘omes from skin microbiome studies, also known as multi’omics. ERVs: endogenous retroviruses.