Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process

Abstract

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.

Truncal acne, what do we know?

“…showed that acne severity on the back is associated with a loss of diversity of C. acnes phylotypes, mainly of phylotype IA1 (95.6%) with a similar prevalence on the face (72.7%). In comparison, on the back of healthy individuals, the percentage of phylotype IA1 was 39.1% IA1 combined with 43.4% of phylotype IAII 18,19 . Moreover, the study confirmed that the A1 SLST‐type, sampled from nodular acne lesions on the back, was predominant.…”

“…Moreover, the study confirmed that the A1 SLST‐type, sampled from nodular acne lesions on the back, was predominant. Thus, the inflammatory mechanism in acne lesions on the back appears very similar to that of facial acne with a loss of diversity of the microbiome activating innate immunity 19 . A previous article provided evidence that innate immunity in normal skin of patients with acne on the back had a different immunity profile in patients with and without acne scars 20 .…”

Deep skin dysbiosis in vitiligo patients: link with mitochondrial and immune changes

“…Examining the bacterial composition of swab microbiota at the genus level, we show that greater than half of taxonomic assignments on skin surface belong to 5 major genera: Staphylococcus, Corynebacterium, Cutibacterium (formerly Propionibacterium ), Kocuria and Paracoccus (Figure 3C). We found a trend for lower Cutibacterium in L compared to NL swabs (p=0.057) (Figure 3C) which may have important implications in vitiligo as the loss of Cutibacterium diversity triggers activation of the innate immune system [11]. We have also seen trends for increased Proteobacteria (p=0.08) phylum in L compared to NL swabs (Figure 3B).…”

Acne treatments: future trajectories

“…In addition, restoration of C. acnes phylotype diversity decreased the inflammatory response of healthy skin explants. 14 In view of these findings, future perspectives in acne treatment imply that modulation of C. acnes phylotypes may be a crucial target in acne. Based on ex vivo findings of modulation of inflammation with monoclonal antibodies to the C. acnes Christie, Atkins, Munch-Peterson (CAMP) factor 2, injection of the CAMP factor-targeted acne vaccine directly into acne lesions, was proposed for potential use in the future.…”

“…acnes phylotypes for maintaining and restoring the cutaneous diversity of C . acnes phylotypes may also be a promising area of research 14 …”