Acta Dermato-Venereologica 99-13CompleteContent | Page 15

CLINICAL REPORT 1253 Safety and Efficacy of Topically Applied Selected Cutibacterium acnes Strains over Five Weeks in Patients with Acne Vulgaris: An Open-label, Pilot Study Ante KAROGLAN 1# , Bernhard PAETZOLD 1,2# , Joao PEREIRA DE LIMA 1,2 , Holger BRÜGGEMANN 3 , Thomas TÜTING 1 , Denny SCHANZE 4 , Marc GÜELL 2,5 and Harald GOLLNICK 1 Department of Dermatology and 4 Institute of Human Genetics, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany, 2 S-Biomedic NV, Beerse, Belgium, 3 Department of Biomedicine, Aarhus University, Aarhus, Denmark, and 5 Department of Health and Experimental Science, Pompeu Fabra University, Barcelona, Spain # These authors contributed equally to this paper. 1 Imbalance in skin microflora, particularly related to certain Cutibacterium acnes strains, may trigger acne. Application of non-acne-causing strains to the skin may modulate the skin microbiome and thereby lead to a reduction in acne. This pilot study evaluates the safety and efficacy of microbiome modulation on acne- prone skin. The study had 2 phases: active induction (5% benzoyl peroxide gel, 7 days) and interventional C. acnes strains treatment (5 weeks). Patients were randomized to either topical skin formulations PT1 (2 strains of C. acnes Single Locus Sequence Typing [SLST] type C3 and K8, 50% each) or PT2 (4 strains of C. acnes SLST type C3 [55%], K8 [5%], A5 [30%] and F4 [10%]). Safety and efficacy was evaluated in 14 pa­ tients (PT1=8/14, PT2=6/14). Skin microbiome com­ position shifted towards study formulations. No un­ toward adverse events, visible irritation, or significant flare-up were observed. Non-inflamed lesions and skin pH were reduced. Comedone counts improved clinical­ ly with no deterioration in inflammatory lesions. Key words: acne vulgaris; microbiome; skin. Accepted Sep 25, 2019; E-published Sep 25, 2019 Acta Derm Venereol 2019; 99: 1253–1257. Corr: Bernhard Pätzold, S-Biomedic, Turnhoutsweg 30, BE-2340 Beerse, Belgium. E-mail: [email protected] A cne vulgaris originates in the pilosebaceous unit of the skin. Increased and modified sebum production, disturbance of follicular keratinocyte differentiation and release of inflammatory mediators are the primary dri- ving forces of acne (1). The second step in the pathogenic cascade is colonization of this unit by Propionibacterium acnes, now known as Cutibacterium acnes, a commensal bacteria, followed by additional triggering of inflam- mation (2, 3). The last decade has not witnessed many therapeutic innovations for acne, nevertheless, newer insights into the pathogenesis of acne is the backbone of current innovations in this field (4). C. acnes is accepted as a trigger for acne, but recent studies utilizing the latest molecular methods reveal that imbalance between the varied microorganisms of the skin microflora and different strains of C. acnes may SIGNIFICANCE This open-label, pilot study enrolled men and women (18– 23 years) with acne vulgaris. In 14 enrolled patients, skin microbiome composition shifted towards study formula- tions. No untoward tolerability, visible irritation, or signi- ficant flare-ups were observed. Non-inflamed lesions and skin pH were reduced. Modulation of Cutibacterium acnes towards the non-acne causing strains on the skin of pa- tients with acne was safe. C. acnes was formerly thought to be the cardinal cause of acne; however, recently some, but not all, strains of C. acnes were found to be responsible. This microbiome modulation approach as therapy requires validation in future clinical studies. explain its role in the disease in greater detail, while leaving the question of cause or consequence unanswe- red (5–7). Studies have also reported that certain strains of C. acnes may trigger endoplasmic reticulum stress (and subsequent apoptosis) that could be attributed to trans-10, cis-12 conjugated linoleic acid produced by linoleic isomerase expressed by these strains (8, 9). Such stress is potentially caused by the activation of lipid mediators (via peroxisome proliferators-activated receptors activation) and contributes to the pathogenesis of acne (9, 10). This led to the hypothesis that replacing the C. acnes strains related to the inflammatory process (high production of linoleic isomerase) on the acne skin with those strains that are not associated (low linoleic isomerase production) with inflammation, might reduce the degree of acne. Moreover, such therapy may help in avoiding the topical and systemic adverse events iden- tified with the currently used therapies, often leading to reduced adherence (11, 12). To address this hypothesis, a proof-of-principle study was conducted in healthy participants in different acne- prone skin areas to demonstrate that new strains of the resident skin microbiota can be successfully transferred to a recipient. The results of this study demonstrate that the composition of the skin microbiome could be mo- dified at the C. acnes strain level within a few days and no major safety events were identified (13). Of note, in microbiome modulation studies unlike traditional studies, This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3323 Acta Derm Venereol 2019; 99: 1253–1257