The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls

Abstract

Importance: Although the pathogenesis of hidradenitis suppurativa (HS) remains enigmatic, several factors point to potential involvement of the cutaneous microbiome. Insight into the cutaneous microbiome in HS using next-generation sequencing may provide novel data on the microbiological diversity of the skin.

Objective: To investigate the follicular skin microbiome in patients with HS and in healthy controls.

Design, setting, and participants: This case-control study obtained punch biopsy specimens from patients with HS (lesional and nonlesional) and healthy controls between October 1, 2014, and August 1, 2016. Data were analyzed from March to November 2016. Patients with HS were recruited from the Department of Dermatology, Zealand University Hospital, Roskilde, Denmark. Biopsy specimens were analyzed at the Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. None of the participants received any antibiotics (systemic or topical therapy) within 1 month before the study. In patients with HS, biopsy specimens were obtained from lesional skin (axilla or groin) and nonlesional skin. Only nodules containing at least 1 visible hair follicle were biopsied. Biopsy specimens from healthy controls were obtained from the axilla only.

Main outcomes and measures: The different microbiomes were investigated using next-generation sequencing targeting 16S and 18S ribosomal RNA.

Results: The skin microbiome was characterized in 30 patients with HS (mean [SD] age, 46.9 [14.0] years; 19 [63% female]) and 24 healthy controls (mean [SD] age, 32.2 [12.0] years; 13 [54% female]). The next-generation sequencing data provided a previously unreported (to our knowledge) characterization of the skin microbiome in HS. The study demonstrated that the microbiome in HS differs significantly from that in healthy controls in lesional and nonlesional skin. Overall, the following 5 microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). In lesional skin, microbiome types consisted predominantly of type I or type IV. Microbiome type IV was not detected in healthy controls. Several taxa, including Propionibacterium, showed a significantly higher relative abundance in healthy controls vs HS skin, indicating that Propionibacterium may be part of the pathogenesis in HS.

Conclusions and relevance: The study findings suggest a link between a dysbiotic cutaneous microbiome and HS.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Saunte reported being paid as a consultant for an advisory board meeting by AbbVie Denmark and reported receiving speaker’s honoraria or grants from the following companies: Bayer, AbbVie Denmark, Desitin, Pfizer, Galderma, Astellas, Novartis, and LEO Pharma. Dr Jemec reported receiving consulting fees from Abbott Laboratories, AstraZeneca, MSD, Novartis, Pfizer, and Dumex-Alpharma; lecture fees from Abbott Laboratories, Galderma, Pfizer, and Roche; grant support from Abbott Laboratories, Pfizer, Photocure, and LEO Pharma; equipment on loan from Michelson Diagnostics; and reimbursement for travel expenses from Abbott Laboratories, Galderma, and Photocure. No other disclosures were reported.

Figures

Figure 1.. Distribution of the Top 10 Most Abundant Species Found in Patients With Hidradenitis Suppurativa (HS) and in Healthy Controls

Shown is the distribution of the 10 most abundant species found in HS lesional skin, HS nonlesional skin, and healthy controls. Overall, the following 5 microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). A and G indicate anatomical location of the samples (axilla or groin).

Figure 2.. Bray-Curtis Principal Coordinates Analysis Plot Showing Differences Between the 3 Groups

Shown are differences between the 3 groups (HS lesional skin, HS nonlesional skin, and healthy controls) in axillary and groin samples. Each lesional sample is connected with its corresponding nonlesional sample. Gray dots indicate samples from the opposite anatomical location (axilla or groin). Ellipses indicate the 75% prediction areas of samples from each group. HS indicates hidradenitis suppurativa.

Figure 3.. Richness Plot and Shannon Diversity Index

A, Richness plot stratified by anatomical location shows no difference between the number of species per sample in the 3 groups (HS lesional skin median [IQR] 72 [59-82], HS nonlesional skin 72 [63-80], and healthy controls 68 [59-78], P = .66) after rarefaction to 5000 reads. No difference was found between the 2 anatomical locations (model comparison with vs without interaction term between group and location, P = .54). B, Shannon Diversity Index stratified by anatomical location shows the diversity of the species in each group. The index reveals an increased diversity in HS nonlesional skin (median [IQR] 3.21 [2.84-3.39]) compared with HS lesional skin and healthy controls (2.80 [2.14-3.09] and 2.52 [1.88-2.95], overall P = .005). No difference was found between the 2 anatomical locations (model comparison with vs without interaction terms between group and location, P = .91). HS indicates hidradenitis suppurativa.

Figure 4.. Differential Abundance Analyses

A, Differential abundance at genus level between hidradenitis suppurativa (HS) lesional skin and healthy controls. Note significantly higher relative abundance of Propionibacterium in healthy controls and significantly higher relative abundance of Porphyromonas and Peptoniphilus. B, Differential abundance at species level between HS lesional skin and healthy controls. Note higher relative abundance of Propionibacterium acnes in healthy controls than in lesional samples. C, Differential abundance at genus level between HS lesional skin and HS nonlesional skin. Note significantly higher relative abundance of Porphyromonas and Peptoniphilus in lesional skin than in nonlesional skin, Propionibacterium is more abundant in nonlesional skin. D, Differential abundance at species level between HS lesional skin and HS nonlesional skin. Note significantly reduced relative abundance of Propionibacterium acnes in HS lesional skin; higher relative abundances of Porphyromonas and Peptoniphilus are found in lesional skin. P values listed are adjusted for anatomical location. Black dots indicate the medians of each distribution.