Propionibacterium acnes, a major member of normal skin microbiota, is subdivided into 6 phylotypes: IA1, IA2, IB, IC, II and III. This study investigated P. acnes subgroups on the face and back in patients with severe acne and in healthy controls. In 71.4% of patients with severe acne, P. acnes phylotypes were identical on the face and back, whereas this was the case in only 45.5% of healthy controls. The healthy group carried phylotypes IA1 (39.1%) and II (43.4%), whereas the acne group carried a high predominance of IA1 (84.4%), especially on the back (95.6%). In addition, the single-locus sequence typing (SLST) method revealed A1 to be the predominant type on the back of patients with acne, compared with a wide diversity in the healthy group. We report here that severity of acne on the back is associated with loss of diversity of P. acnes phylotype, with a major predominance of phylotype IA1. The change in balance of cutaneous P. acnes subgroups might be an inducing factor in the activation of P. acnes, which could trigger inflammation.

Background Acne has long been understood as a multifactorial chronic inflammatory disease of the pilosebaceous follicle, where Cutibacterium acnes (subdivided into six main phylotypes) is a crucial factor. In parallel, the loss of microbial diversity among the skin commensal communities has recently been shown as often accompanied by inflammatory skin disorders. Objective This study investigated the association of C. acnes phylotype diversity loss and the impact on Innate Immune System (IIS) activation. Methods The IIS response of skin after incubation with phylotypes IA1, II or III individually and with the combination of IA1 + II + III phylotypes, was studied in an in vitro skin explant system. The inflammatory response was monitored by immunohistochemistry and ELISA assays, targeting a selection of Innate Immune Markers (IIMs) (IL‐6, IL‐8, IL‐10, IL‐17, TGF‐β). Results IIMs were significantly upregulated in skin when being incubated with phylotype IA1 alone compared with the combination IA1 + II + III. In parallel, ELISA assays confirmed these results in supernatants for IL‐17, IL‐8 and IL‐10. Conclusion We identify the loss of C. acnes phylotype diversity as a trigger for IIS activation, leading to cutaneous inflammation. These innovative data underline the possibility to set up new approaches to treat acne. Indeed, maintaining the balance between the different phylotypes of C. acnes may be an interesting target for the development of drugs.

Acne is the most common inflammatory dermatosis, affecting up to 85% of the 11-30 years old world population. [1] This disease is subdivided according to severity graduation, from minor to severe acne, and affects different body localizations from face to back. [2] The mechanisms leading to severe acne, representing up to 20% of acne patients, are still poorly understood, although Cutibacterium acnes (C. acnes) appears as a key player of acne physiopathology.Recently, an increasing interest was observed related to skin microbiota's impact on innate immunity, and subsequently, on inflammatory dermatoses physiopathology. [3,4] Two major studies previously decrypted skin microbiota in acne context; however, this topic remains poorly documented-especially on the back-and the sampling methodologies used were quite controversial. [5][6][7] Indeed, Barnard et al and Fitz-Gibbon et al both described skin microbiome in acne and healthy context, using strip from nose of patients. [8,9] These studies both showed that no clear difference was observed in C. acnes abundance between healthy and acne individuals, whereas recent evidences highlighted a loss of C. acnes subgroups diversity in severe acne context. [10] On the other hand, studying skin bacterial populations using either 16S metataxonomic method or shotgun, to reveal the skin microbial composition, have never been described before in severe back acne context. The present study aims to investigate skin microbiota in patients with severe acne of the back vs healthy controls, sampling two major localizations of acne lesions: the back and the face. | MATERIAL AND ME THODS | Recruitment of healthy volunteers and patientsIn the present clinical study, 24 patients with severe acne of the back and 12 healthy volunteers were enrolled. Regarding the skin type, all Abstract Acne is the most common inflammatory skin disease, affecting up to 85% of the 11-30 years old world population. Skin microbiota appears as a key player involved in several skin dermatoses physiopathology. Here, we show that inflammatory skin is associated with changes in the skin microbiota composition on the back of severe acne patients but also on the face of patients where acne was scored as mild to moderate, comparing with healthy controls. Changes were observed particularly on skin commensals Propionibacteriaceae, Staphylococcaceae and Enterococcaceae families, suggesting the importance of the balance between skin commensals to maintain skin homeostasis and control skin inflammatory process. K E Y W O R D Sacne, inflammatory skin diseases, innate immunity, microbiology, microbiome

Background Acne fulminans (AF) is a rare and severe form of inflammatory acne. It is characterized by a sudden worsening of acne with appearance of ulceronecrotic lesions, which can be associated with systemic signs. Its pathophysiology and the best therapeutic strategy are only partially known. Objective Our main objectives were to describe the clinical and biological profile of AF patients and to determine whether there was a difference in Cutibacterium acnes phylotype in AF compared to acne vulgaris. The secondary objective was to assess the efficacy of different therapies. Methods A retrospective observational study was conducted in all patients followed for AF in our department between 2008 and 2018. Bacteriological samples were taken from each patient to analyse C. acnes phylotype distribution. The therapeutic response was assessed using the ECLA and GEA scales. Results Fifteen patients with a median age of 15 years were included (12 men, 80%). A family history of acne was found in 86.7% of patients. Nine patients (60%) had isotretinoin‐induced AF. Only one patient (6.7%) showed systemic signs. The bacteriological culture was positive for C. acnes in 80% of patients. The predominant phylotype was IA1 in 60% of patients, corresponding to the predominant phylotype in acne vulgaris. Only 33.3% of patients were in remission after a first‐line treatment with systemic corticosteroids, alone or in combination. Seven patients were treated with biotherapy, including five successfully with secukinumab. Conclusion Our results suggest that there is no specific C. acnes phylotype associated with AF, raising the hypothesis that acute inflammation associated with AF may be more related to an abnormal cutaneous innate immunity activation. The use of preventive strategies, the impact of combined treatments and an assessment of the role of biotherapies, especially anti‐IL‐17, in AF treatment remain to be more investigated.

There is an obvious need to create a consensus about molecular typing methods for C. acnes. This standardization will facilitate the comparison of results between one article and another, and also the interpretation of clinical data.

Bacterial extracellular vesicles (EVs) are bilayered lipid membrane structures, bearing integral proteins and able to carry diverse cargo outside the cell to distant sites. In microorganisms, EVs carry several types of molecules: proteins, glycoproteins, mRNAs and small RNA species, as mammalian EVs do, but also carbohydrates. Studying EVs opens a whole new world of possibilities to better understand the interplay between host and bacteria crosstalks, although there are still many questions to be answered in the field, especially when it comes to microbiota-derived EVs. In this review, we propose to summarize and analyse the current literature about bacterial EVs and possible clinical applications, through answering three main questions: (a) What are bacterial EVs? (b) What are EV impacts on skin inflammatory disease physiopathology? (iii) What are the possible and expected clinical applications of EVs to treat inflammatory skin diseases? K E Y W O R D S cell-to-cell communication, exosomes, extracellular vesicles, microbiota, probiotics, skin microbiota | 23 DAGNELIE Et AL.

Acne is a multifactorial inflammatory dermatose that affects all age categories from teenagers to adults, resulting in important psychological impacts. Multiple hypotheses currently attempt to decrypt the physiopathology of this disease, and four main actors were identified as highly implicated in it: hyperkeratinization of the pilosebaceous follicle, hyperseborrheae, host factors (innate immunity) and skin microbiota. In this letter, we present results illustrating the impact of skin microbiota on inflammatory skin response, and how far the proper balance between each bacterial community, especially C. acnes and S. epidermidis, is crucial to maintain an appropriate inflammatory response on the skin. The data presented in this study demonstrate that within the skin microbiota, an imbalance between Cutibacterium acnes and Staphylococcus epidermidis, is able to induce the activation of inflammation‐related markers such as IL‐1ra, IL‐6, IL‐8, G‐CSF and the molecules C5/C5a, soluble CD14 MIP‐3beta, Serpin E1, VCAM‐1 and beta‐defensin‐2. Moreover, S. epidermidis appears to have a more important role than C. acnes on the induction of inflammation‐related markers, particularly on IL‐6. This work is the basis of future in vitro studies to further understand acne physiopathology, inspiring the development of future innovative therapies based on skin microbiota modulation.

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