914 Cutibacterium acnes phylotypes diversity loss: A trigger for skin inflammation process

Acne has long been understood as a multifactorial inflammatory disease where Cutibacterium acnes is a crucial actor, subdivided into 6 phylotypes (IA1, IA2, IB, IC, II and III). Recent clinical investigations on C. acnes populations shed the light on an interesting observation: a drastic loss of phylotype diversity is found in severe acne patients comparing with healthy individuals. We raise the hypothesis that the C. acnes phylotype diversity loss can be a trigger for inducing skin inflammation. We compared the modulating effect on innate immunity of each C. acnes phylotypes IA1, II, and III individually, to a mixture of several phylotypes mimicking the diversity of the normal microbiote (IA1+II+III). After coculture with healthy skin explants, we measured the inflammatory responses in skin between each condition by immunohistochemistry and ELISA assays, targeting a panel of innate immune markers (IIMs). Most of the tested IIMs were upregulated in skin when being incubated with phylotype IA1 alone comparing with the mixture IA1+II+III (IL-17, p < 0.00290 ; IL-1β, p < 0.0374 ; IL-10, p < 0.00630 ; TLR-2, p < 0.00406 ; β-defensin-2, p < 0.00290). In parallel, ELISA assays confirmed these results in supernatants for IL-17, IL-8, and IL-10. Constant crosstalks between the skin and commensal microorganisms regulate local immune responses to ensure efficient skin functions and prevent chronic diseases. Here, we report that the loss of C. acnes phylotype diversity is one of the main mechanisms for the activation of skin innate immunity. These results provide new paradigms for the mechanisms that trigger skin inflammation and they depict key data to develop future therapeutic options.