Bacterial porphyrins in healthy skin: Microbiota components impact melanogenesis and age‐related processes leading to Porphyr'ageing

Porphyrins are ubiquitous metabolites and are constitutive of the bacterial metabolome of healthy skin. Their consideration has until now been limited to their pro-inflammatory activity in acne vulgaris. The present work suggests a new role for these molecules in the onset of skin ageing. A mixture of coproporphyrin III and protoporphyrin IX, representative of skin microbiota metabolites, was defined and applied in different skin models. Finally, an in vivo study was conducted to determine the association between porphyrin's abundance and ageing signs. Bacterial porphyrins penetrated stratum corneum and reached living epidermal cells. The porphyrin mixture increased IL-8, ROS and melanin contents. Porphyrin-induced melanin synthesis appeared to be regulated by translocator protein TSPO/PBR. In fibroblasts, bacterial metabolites down-regulated a set of transcripts involved in extracellular matrix architecture and associated with ageing, which was confirmed by a decrease of type I pro-collagen. Finally, the clinical study established positive and significant correlations between porphyrin abundance and the severity of ageing signs, including invisible spots, brown spots and wrinkles length. In summary, porphyrins could play unexpected roles in skin's premature ageing process, a phenomenon we propose to call Porphyr'ageing, that promotes hyperpigmentation, inflammation, oxidative stress and fibroblast cell ageing, leading to dermal matrix weakening.