Characterization and Analysis of the Skin Microbiota in Rosacea: Impact of Systemic Antibiotics

Abstract

Systemic antibiotics are extensively used to control the papules and pustules of rosacea. Hence, it is crucial to understand their impact on the rosacea skin microbiota which is thought to be perturbed. The purpose of this study was to compare the makeup and diversity of the skin microbiota in rosacea before and after taking oral antibiotics. We also compared the skin microbiota at baseline according to age and rosacea severity. A longitudinal cohort study was performed on 12 rosacea patients with papules/pustules and no recent use of oral and topical antimicrobials/retinoids. Patients were prescribed oral doxycycline, 100 mg, twice daily for six weeks. Skin areas on the cheek and nose were sampled for 16S ribosomal RNA gene sequencing at baseline, and after six weeks of doxycycline treatment. Eleven females and one male aged 20–79 (median 51) with a median Investigator’s Global Assessment score of 3 (moderate) were enrolled. At baseline, Staphylococcus epidermidis was the most dominant species followed by Cutibacterium acnes (formerly Propionibacterium acnes). In the 60 Over-age group, the prevalence of Cutibacterium acnes was lower than that of the 60 & Under-age group. Rosacea severity increased with age and was associated with a decrease in the relative abundance of Cutibacterium acnes and an increase of Snodgrassella alvi. Across all subjects, antibiotic treatment reduced clinical rosacea grades and was associated with an increase in the relative abundance of Weissella confusa (P = 0.008, 95% CI 0.13% to 0.61%). Bacterial diversity (alpha diversity) was not significantly altered by antibiotics treatment. Principal coordinates analysis showed mild clustering of samples by patient (ANOSIM, Analysis of Similarity, R = 0.119, P = 0.16) and scant clustering with treatment (ANOSIM, R = 0.002; P = 0.5). In conclusion, we believe that rosacea has a unique age-dependent characteristic (i.e., severity). Although we were not able to pinpoint a causative microbiota, our study provides a glimpse into the skin microbiota in rosacea and its modulation by systemic antibiotics.

Microbiota in Rosacea

“…The relative abundance of C. acnes in Caucasians with rosacea has been found to be lower in older patients (females aged 50 years and over, and males aged over 55) than in their younger counterparts [19]. My team also confirmed that the relative abundance of C. acnes in Asian rosacea patients was lower in those aged over 60 compared to those aged 60 and under (18-fold difference, P = 0.018) [22]. When the cut-off age was set at 50 years, S. epidermidis was the predominant species in Asians aged under 50 (42%), followed by C. acnes (16%), and Acinetobacter haemolyticus (13%).…”

“…This was followed by C. acnes (22%) in patients with severe rosacea, and by P. koreensis (16%), S. alvi (12%), and Corynebacterium tuberculostearicum (11%) in patients with moderate rosacea. S. alvi was significantly more abundant (P = 0.0081) [22] in patients with severe rosacea than in those with moderate rosacea. Conversely, a lower relative abundance of C. acnes (P = 0.0087) [22] was seen in patients with severe rosacea.…”

“…S. alvi was significantly more abundant (P = 0.0081) [22] in patients with severe rosacea than in those with moderate rosacea. Conversely, a lower relative abundance of C. acnes (P = 0.0087) [22] was seen in patients with severe rosacea. Although not statistically significant, a linear regression analyses performed by Rainer et al [19] showed a weak negative correlation between C. acnes abundance (P = 0.124) and rosacea severity (NRS), together with a positive correlation between C. kroppenstedtii abundance (P = 0.065) and severity.…”

“…The microbial composition of the skin has been examined according to rosacea severity. My group [22] found S. epidermidis to be predominant in patients with both moderate (38%) and severe (17%) rosacea, with respective grades of 3 and 4 on the 5-point Investigator's Global Assessment (IGA) grading scale. This was followed by C. acnes (22%) in patients with severe rosacea, and by P. koreensis (16%), S. alvi (12%), and Corynebacterium tuberculostearicum (11%) in patients with moderate rosacea.…”

“…Only Geobacillus and Gordonia remained significantly associated with rosacea severity after a multivariate random effect Poisson regression analysis. Unlike acne, rosacea usually progresses/worsens over time [18] and it is likely that the negative correlation of C. acnes and the positive association of S. alvi with rosacea severity [22] is in part due to age. Interestingly, S. alvi has been identified in Demodex mites from both rosacea patients (ETR and PPR) and healthy controls [20].…”