Over the past several years, the skin microbiome has emerged as an important research field of interest for human health and personal care. In a previous 2021 blog post, we touched on some of the commercial opportunities in the skin microbiome research space; specifically, how existing research intersects with skincare and beauty products. We thought it might be a good time to revisit the skin microbiome literature to review how much has changed, including current challenges and advances in research. 

A refresher on the skin microbiome and why it matters  

Skin—the largest organ of the body—can be colonized by a diverse range of microorganisms.¹ The skin microbiome is defined as the complete collection of microorganisms inhabiting the skin at a specified time. Importantly, the composition of the microbial communities associated with skin has been shown to change between infancy to adulthood,² and correlate with human health and disease states.¹ Human skin can be classified into three main types based on physiological characteristics with each skin type showing a distinct microbial composition based on site.¹ These three types are:

1. Dry (e.g., forearm and palm)
2. Wet/moist (e.g., bend of elbow, back of knee, and groin)
3. Sebaceous or oily (e.g., face, torso, and back)

To study the skin microbiome, specific microorganisms were initially isolated from skin samples and grown in laboratory cultures. This method however introduces bias as it favors the study of microorganisms (typically bacteria) amenable to culture-based approaches and is not representative of the true diversity of the skin microbiome.^1,2 More recent study methods have focused on sequencing skin samples (e.g., 16S ribosomal RNA sequencing, shotgun metagenomic sequencing, third generation long-read sequencing, etc.) directly from the site of interest.^1,2 Although sequencing is a promising approach, it is not without its own potential limitations. For example, there is some concern that sequencing technologies may overestimate species richness and diversity due to sequencing more than the targeted viable bacterial DNA (e.g., widely utilized sequencing techniques may also capture extracellular DNA).² 

In terms of bacterial density, the human skin microbiome is second only to the gut microbiome.² Generally, researchers have found that—similar to gut microbiome studies—changes in the skin microbiota (typically a balance of so-called “good” bacteria versus pathogenic or “bad” bacteria) are associated with several common skin diseases and disorders.¹ This imbalance or alteration of the microbiota is referred to as dysbiosis—an altered microbial composition compared to the normal state.¹ Aside from skin diseases, scientists have also sought to determine whether there are correlations between the skin microbiome and aging (reviewed in ²). Since our skin is often the first line of defense between our body and the outside world, studying the skin microbiome and how it plays a role in our systems’ biology is important to overall human health research along with the gut microbiome. 

Key research advances in skin microbiome research 

Although several open-access peer-reviewed articles have been published in recent years, in this current blog post, we briefly wanted to highlight three recent papers of interest. The first article, published in 2021 in Science Translational Medicine, was a medical-focused study that assessed the skin microbiome (in addition to the oral and gut microbiomes) after systematic antibiotic use.³ The skin focus of this study was especially interesting as previous efforts have mostly focused on studying the effect of antibiotics on the gut microbiome. 

In their small pilot study, the researchers randomly gave healthy participants a commonly-prescribed systemic oral antibiotic (i.e., doxycycline, cephalexin, or trimethoprim/sulfamethoxazole) and then sampled their skin (across three skin sites), oral, and gut microbiota at several time points up to a year after antibiotic administration.³ The key findings, with implications for prescribing oral systemic antibiotics, were that antibiotics can: 

1. Alter the skin microbiota, and this can be site- and individual-specific. This result also supports previous findings that indicate that oral antibiotic use can induce skin microbiota dysbiosis. 
2. Have an enduring effect on the skin microbiome (e.g., ranging from 42 days to beyond 200 days of persistent microbial alterations).³ 
   
3. Lead to antibiotic (in this study, doxycycline, specifically) resistance in some specific bacterial species that have colonized the skin. 

The second article we are going to discuss is a more recent 2023 paper, published in Microbiology Spectrum, that specifically focused on assessing the different environmental components needed for various skin microbial species to thrive under the harsh and stressful conditions of human skin (e.g., low pH, low nutrient availability, etc.).⁴ The study was of particular interest as the researchers were able to provide a rationale for why different skin sites are composed of unique microbial communities.⁴ They also used their findings to create a synthetic skin-like bacterial growth culturing media, valuable for conducting physiologically relevant microbial studies involving culturing in the laboratory.⁴  

The final article selected for our review is a recent publication, published May 2023, in the MDPI Microorganisms journal, written by our own team of experts from DNA Genotek and Diversigen (our sister company and another subsidiary company of OraSure Technologies).⁵ In this review paper, our scientists review in detail the: 

• Methodological steps associated with study design, skin sample collection, storage, processing, and bioinformatics analysis of bacterial skin species. 
• Current sequencing approaches (i.e., shotgun metagenomics, whole 16S rRNA gene sequencing, and metatranscriptomics).  
• Technical challenges, including the importance of experimental controls to avoid cross-contamination. 
  
• Future areas of research and applications pertaining to the skin microbiome (e.g., developing therapeutics and diagnostics, forensic applications, etc.).

Image from Santiago-Rodriguez et al., 2023, Figure 1, published in Microorganisms.⁵ 

Addressing skin sample collection challenges for skin microbiome research 

As we previously alluded to, there are several challenges currently hindering the study of the skin microbiome. First, it can be difficult to acquire enough nucleic acid content from low microbial biomass skin sites to be used consistently in downstream applications. Second, because of biases introduced during collection, it can be difficult to get an accurate and true representation of the skin microbiome. For both reasons, the collection aspect is a critical first step in ensuring the skin sample acquired provides an accurate and true representation of the skin microbial composition.  

DNA Genotek—a subsidiary company of OraSure Technologies Inc.—offers a skin sample collection device for skin microbiome profiling that can address several sample collection challenges. 

OMNIgene™•SKIN is an all-in-one system for the collection, stabilization, transportation, and storage of microbial DNA from skin samples. Capable of stabilizing bacterial and fungal profiles at point-of-collection from all skin types (i.e., dry, wet, and sebaceous) by minimizing biases introduced by microbial growth and DNA degradation, the device allows for the collection and stabilization of microbial DNA for a more accurate representation of the skin microbiome.⁶  

In terms of added benefits, because this device maintains microbial profiles throughout temperature fluctuations encountered during real-life shipping and handling conditions (e.g., -20°C to +50°C) and does not require immediate freezer storage and cold-chain transport,6 skin samples can be collected globally. A second benefit is that this device includes intuitive and easy-to-follow user instructions for sample collection; straightforward steps for use make it easier for users to successfully collect skin samples and could lead to improved participant compliance in research studies.  

Concluding remarks and takeaways 

Though the skin microbiome research field is still in its early stages, most researchers are already well-versed in the challenges. These challenges can range from issues associated with study design such as participant recruitment to technical challenges like acquiring adequate biomass from skin sample collection (including removal of host DNA) or whether to conduct targeted or untargeted sequencing, to the desire to produce reproducible, quality data that is an accurate and true representation of the skin microbiome.  

DNA Genotek is pleased to be able to offer a tried-and-tested product that can assist researchers in the collection aspect for their skin samples. To see for yourself if the OMNIgene™•SKIN product is right for your laboratory workflow, please click the purple button below to request a free trial kit. 

References

1. Byrd AL, Belkaid Y, Segre JA. (2018) The human skin microbiome. Nature Rev Microbiol. doi: 10.1038/nrmicro.2017.157 

2. Smythe P, Wilkinson HN. (2023) The skin microbiome: current landscape and future opportunities. Int J Mol Sci. doi: 10.3390/ijms24043950 

3. Jo JH, Harkins CP, Schwardt, N. H., Portillo, JA, NISC Comparative Sequencing Program, Zimmerman MD, Carter CL, Hossen MA, Peer CJ, Polley EC, Dartois V, Figg WD, Moutsopoulos NM, Segre JA, Kong HH. (2021) Alterations of human skin microbiome and expansion of antimicrobial resistance after systemic antibiotics. Sci Transl Med. doi: 10.1126/scitranslmed.abd8077 

4. Swaney MH, Nelsen A, Sandstrom S, Kalan LR. (2023) Sweat and sebum preferences of the human skin microbiota. Microbiol Spectr. doi: 10.1128/spectrum.04180-22 

5. Santiago-Rodriguez TM, Le François B, Macklaim JM, Doukhanine E, Hollister EB. (2023) The skin microbiome: current techniques, challenges, and future directions. Microorganisms. doi: 10.3390/microorganisms11051222 

6. Bouevitch A, Macklaim J, Le François, Brice. (2020) OMNIgene™•SKIN (OMR-140): an optimized collection device for the capture and stabilization of the human skin microbiome. [White paper]