Distinct Intraspecies Variation of Cutibacterium acnes and Staphylococcus epidermidis in Acne Vulgaris and Healthy Skin

Abstract

Human skin hosts a diverse array of microorganisms that contribute to its health. Key players in the facial skin microbiome include Cutibacterium acnes and staphylococci, whose colonization patterns may influence dermatological conditions like acne vulgaris. This study examined the facial microbiome composition of 29 individuals, including 14 with moderate to severe acne and 15 with healthy skin, using single locus sequence typing (SLST) amplicon sequencing. The results showed a shift in the relative abundances of C. acnes phylotypes: SLST types A, C, and F were increased in acne, while types H, K, and L were reduced compared to healthy skin. Among staphylococci, the relative abundance of S. epidermidis, S. capitis, and S. saphrophyticus increased in acne, while S. saccharolyticus and S. hominis decreased. The amplicon sequencing approach could also identify a population shift of S. epidermidis: a specific S. epidermidis phylogenetic lineage (type 3) was reduced in acne, while two abundant lineages (types 1 and 2) were elevated. These findings suggest that distinct phylogenetic lineages of both C. acnes and S. epidermidis are linked to healthy versus diseased skin, highlighting a potential role for both microorganisms in disease prevention and aggravation, respectively.

Keywords: Cutibacterium acnes; Staphylococcus; Staphylococcus epidermidis; acne vulgaris; amplicon-based next-generation sequencing; skin microbiome.

Figure 1

C. acnes phylotype composition in the healthy and acne cohort. (A) SLST amplicon sequencing results of 15 and 14 skin swab samples from healthy individuals and acne patients, respectively. (B) Mean relative abundance of the different C. acnes SLST types for the two cohorts. HS, healthy skin; AS, acneic skin. (C) Mean relative abundance of the different C. acnes SLST classes for the two cohorts. (D) Boxplots for the seven most prevalent SLST classes, showing the variation across samples. The midline of the boxplot represents the median, the upper line represents the upper quartile, and the lower line represents the lower quartile. Wilcoxon rank-sum test; ***: p-value < 0.001; **: p-value < 0.01; *: p-value < 0.05; ns, non-significant (p-values: A, 0.0846; C, 0.0004; D, 0.2242; F, 0.0724; H, 0.0076; K, 0.0209; L, 0.2241). (E) Shannon diversity index (alpha diversity) for the C. acnes population in the acne cohort compared to the healthy cohort. Wilcoxon rank-sum test (p-value 0.78).

Figure 2

Staphylococcal community composition in the healthy and acne cohort. (A) tuf2 amplicon sequencing results of 15 and 14 skin swab samples from healthy individuals and acne patients, respectively. (B) Mean relative abundances of the main staphylococcal species in the two cohorts. HS, healthy skin; AS, acneic skin. (C) The composition of the staphylococcal population according to the main identified tuf2 alleles. Some species are represented by more than one tuf2 allele, e.g., S. epidermidis with four tuf2 alleles. (D) Mean relative abundance of the staphylococcal population at the subtype level of the two cohorts. (E) Boxplots for the 10 most prevalent staphylococcal tuf2 alleles, showing the variation across samples. The midline of the boxplot represents the median, the upper line represents the upper quartile, and the lower line represents the lower quartile. The Wilcoxon rank-sum test showed no significant difference between HS and AS. (F) Shannon diversity index (alpha diversity) for the staphylococcal population in the acne cohort compared to the healthy cohort. Wilcoxon rank-sum (p-value, 0.1023).

Figure 3

The staphylococcal tuf2 gene fragment can serve as a phylogenetic marker of S. epidermidis. (A) The tuf2 sequences were extracted from 69 S. epidermidis genomes (taken from [17]) and phylogenetically compared. Five tuf2 alleles were found among the 69 strains (alleles (=types) 2–5 are color-coded (type 2, yellow; type 3, green; type 4, blue; type 5, red; type 1 is not color-coded). Bootstrap support (in %) is added to the branches. (B) Core genome phylogeny was reconstructed from the 69 S. epidermidis strains. Strains were color-coded according to their tuf2 alleles (color-code see (A)). Some phylogenetically distinct lineages are represented by different tuf2 alleles, e.g., types 2, 3, and 4. Types 1 and 5 are intermixed.