The Role of the Skin Microbiota in Acne Pathophysiology

S. Ramasamy; E. Barnard; T.L. Dawson Jr; H. Li

Disclosures

The British Journal of Dermatology. 2019;181(4):691-699. 

In This Article

Microbial Dysbiosis in Acne

The mechanisms contributing to interactions between microbiota and host factors remain to be defined. Microbial dysbiosis of C. acnes, Malassezia, bacteriophages, and perhaps other microbes, coupled with disturbed skin barrier formation and immune responses, are all factors correlated with acne.[43,61,62] A recent metagenomic study that compared acne skin with healthy skin revealed that the balance among bacterial, fungal and bacteriophage components was important in the maintenance of skin health.[11,66] Microbial dysbiosis can influence innate immunity through multiple targets, which include peroxisome proliferator-activated receptors, interferon signalling, tumour necrosis factor activation, ILs and Toll-like receptors. Matrix metalloprotease activity, being one of the factors of innate immunity response to C. acnes, has also been proposed as a cause of hyperkeratinization in pilosebaceous units, which is important for acne pathogenesis.[7,67] The classical aetiological stepwise process has been challenged after review of recent studies where inflammatory dysregulation precedes C. acnes and biofilm formation, before formation and maturation of comedones.[68] The interaction of the immune system with C. acnes and pathogenesis of acne is important for the development of effective vaccine strategies.[69–71] Other reports suggest a role for a C. acnes-secreted 'biological glue' in cohesion of biofilms and potentially holding keratinocytes together to form the microcomedones.[68,72,73] Hence, it is important to establish a timeline to study microbial dysbiosis events that lead to acne pathophysiology.

Sampling Methods and Study Design Influence Interpretation

The method utilized to obtain clinical samples defines the described character of the resulting pathophysiology-associated microbiome. The methods used for follicular microbiome sampling remain controversial and require careful consideration when chosen to address specific questions.[28,29,74–77] The primary challenge is to collect samples that exclusively depict acne pathophysiology (Figure 1 and Table 2). For example, where do we sample for acne and at what stage (prelesional vs. lesional)? Specifically, most acne microbiome studies are based on surface sampling and/or have sampled the lesion exudate. However, it is likely that in order to make an accurate prediction of the role of microbiota in acne pathogenesis, it would be necessary to sample from the infrainfundibular sebocellular junction (Figure 1 and Table 2). Ideally, it would be beneficial to collect samples prior to, during, and after lesion development, but the obvious difficulty in collection from this site at these times remains challenging. However, sample collection of acne-specific lesions from deep sites in dilated hair follicles may represent a more descriptive total hair follicle compartment microbiome. So it is important to consider the transitory movement of C. acnes strains in the infundibular zone and the inflamed sebocellular compartment (Figure 1). One must fully consider the disease stage, depth of resident microbiota, topography of the pilosebaceous unit and the sebaceous environment.

Sebaceous follicles, which are generally recognized as the site where acne originates, were once considered to represent a uniquely harsh environment for bacteria that can only support C. acnes colonization in healthy individuals.[78] However, heterogeneity was often found in previous culture-based studies of healthy follicles owing to differences in sampling.[78] Each method has its own advantages and is uniquely suitable for specific purposes. Swabbing samples only the skin surface and does not extend into the pilosebaceous unit, which is key to gaining a full understanding of acne development and progression. Surface sampling methods do not access internal anaerobic sites where acne structures are common. Surface sampling also covers a larger area and has the potential to sample both diseased and healthy areas. Microdissection of single pilosebaceous units from punch biopsy specimens is invasive and may result in contamination with skin surface colonizers. The pore strip and cyanoacrylate biopsy have the advantages of being noninvasive, capturing the upper stratum, and isolating the pilosebaceous unit via dissection, thereby minimizing the potential for surface contamination.[78] A recent study compared sampling using surface swabs, pore strips and cyanoacrylate glue follicular biopsy.[79] While differences exist, overall, the relative abundance of bacterial and fungal species and the taxonomic diversity detected were similar. However, the viral composition was different on the surface and in the follicle. Studies such as this, which take advantage of multiple sampling methodologies, will be essential for clarifying microbial involvement in acne pathogenesis and progression.

It is also necessary to consider and implement suitable study designs and validate appropriate sampling according to the specific needs defined by skin and pathophysiology. The design should include consideration of potential confounding factors, such as patient demographics, medical history, antibiotic and cosmetic use, site and surface topography, relevant anatomical structure, and selection of appropriate sampling tools and sites.[80] Contamination is also a very common issue in skin microbiome studies, as the microbial biomass is limited. Often a large number of participants and samples are required to achieve sufficient statistical power to arrive at meaningful results. In summary, although sampling the skin surface rather than the follicle has been common in acne publications, it is often the parameter of choice, usually for reasons of expediency rather than technical robustness. It is important to consider the methods specific to the disease state, the disease anatomy and the questions to be investigated. Although a variety of studies address different sampling methods at specific sites, establishing the importance of individual sites of pathophysiological significance in specific longitudinal stages, ideally occurring before lesion development or at least in the same site after regression, will be necessary to address the role of microbiota in acne.

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