In medicine, we have long recognized that the microbial communities in our bodies and on our skin are intricately linked to health and disease. Acne vulgaris is a disease that exemplifies the importance of host-microbiome interactions in disease pathogenesis. It is one of the most common skin diseases worldwide, with rates of up to 85% among 12- to 24 year-olds.1 Though the pathogenesis of acne is multifactorial, our understanding of acne is expanding with recent advances from studies on the microbiome. The skin microbiome is collectively composed of a complex community of bacteria, fungi, viruses, and microscopic arthropods that inhabit all skin surfaces and appear to have unique functions on the skin.2 By culturing and sequencing of these microbial inhabitants, studies have confirmed topographical diversity of the bacterial communities on our skin.3 Sebaceous areas favor the growth of the lipophilic Cutibacterium species, formerly known as Propionibacterium.4
Cutibacterium acnes has long been implicated as a pathogenic factor in acne. Yet, it is also a major commensal of the normal skin microbiome. Contrary to popular belief, C acnes overgrowth does not correlate with acne development and severity; acne-affected skin does not harbor more C acnes than normal skin. Genomic analyses have confirmed that C acnes is dominant in the pilosebaceous units in both patients with acne and individuals with normal skin, with no significant difference in the relative abundance between these two cohorts.5 Thus, research is now focusing on the specific composition of C acnes strains within the acne microbiome and the host interactions, affecting both the innate and adaptive immune responses.
DNA sequencing-based methods used for bacterial typing have now allowed for identification of distinct C acnes phylogenic groups, classifying strains with different genetic lineages into types I, II, and III. Various molecular typing methods use different nomenclature to further subdivide strains into clonal complexes, phylotypes, and ribotype denominations.6,7 Typing of C acnes strains has taken on increased importance due to the emerging clinical relevance of differences between strains. Multiple research groups have investigated the association of different C acnes types with acne and revealed distinct patterns. It appears that while the majority of strains are found in both patients with acne and individuals with normal skin, there are indeed specific C acnes strains more highly associated with acne, while others are exclusively associated with healthy skin. Since the 1980s, it has been known that type I C acnes are more associated with acne than type II.8 Through sequence comparisons of the C acnes 16S rRNA gene in patients with acne vs normal controls, Fitz-Gibbon et al5 found that certain ribotypes (designated ribotypes 4, 5, 8, and 10) were statistically significantly enriched in acne patients, whereas ribotype 6 was strongly associated with healthy skin.5 Lomholt et al9 also found that the dominating C acnes clones in follicles from patients with acne were exclusively from the phylogenic clade I-1a and all belonged to corresponding ribotypes 4 and 5.9 Interestingly, phylotype III bacteria compose approximately 20% of isolates from healthy skin but have not been found in acne lesions.10 Thus, by correlating association data based on different typing systems, it is clear that IA-2 strains with a plasmid factor, IB-1, and I-C phylotypes of C acnes are associated with acne, while ribotype 6 strains within phylotype II, as well as phylotype III, are associated with healthy skin.6
These disease associations then beg the question of why? There is evidence to suggest that they may be related to specific phenotypic and functional differences among C acnes strains, which have implications in disease pathogenesis. Metagenomic analyses revealed that distinct virulence-associated genomic elements of tissue degradation and cell adhesion are enriched in acne-associated C acnes strains.11 Proteomic studies using mass spectrometry also demonstrate differential protein expression of adhesion proteins, CAMP factors, proteases, and lipases.12 Healthy skin-associated phylotype II strains possess a clustered regularly interspaced palindromic repeats (CRISPR)-Cas locus, which is protective against viruses and acquisition of foreign DNA that could promote virulence. This CRISPR-Cas locus is also partially present in healthy skin-associated phylotype III, but is absent in type I acne-associated strains.13 Furthermore, C acnes phylotypes exhibit differences in inflammatory potential. In vitro studies have shown that acne-associated phylotypes induce high T helper (TH) 1 and TH17 responses, while healthy skin-associated phylotypes induce relatively lower TH1 and TH17 responses but a higher IL-10 anti-inflammatory response.12 Therefore, accumulating evidence suggests that certain phylotypes of C acnes and their host interactions play a central role in this chronic inflammatory condition. Further investigations are needed to gain better insight into strain-specific factors that may impact inflammatory response, acne severity, and distribution patterns in different acne lesions.