The role of the skin microbiome in the development of skin fibrosis in SSc

Skin fibrosis with disfigurement and functional impairment substantially contributes to the disease burden. Early mechanisms of skin fibrosis are inflammation-dependent with dysregulation of innate immunity playing as a pathogenic key factor.

Recent research efforts have provided important insights into the role of commensal bacteria
in health and disease. In addition to advanced work on the gut microbiome, novel data suggest that the skin microbiome might play an important role in various diseases. There is increasing evidence that the skin commensal bacteria affect the development of the (epi-)der¬mal immune system and the physical barrier. This suggests a cross-talk with host cells in deeper layers of the epidermis and dermis, especially since many cell types in the dermis express functional pattern recognition receptors with active responses upon stimulation with microbial components in vitro, which could indicate a penetration of the basement membrane of the epidermis by microbes or microbial products. Of note, a very recent study provided evidence for a previously unknown physical interaction between commensal bacteria and dermal cells since bacterial components were ubiquitously detectable throughout the dermis.

In our study, we aim to assess whether the skin microbiome plays a direct role in the activation of the innate immune system and might thereby contribute to the development of skin fibrosis in SSc. Interestingly, myofibroblasts have been shown to act as antigenpresenting cells, to become activated by bacterial products or other alarm signals and to have a functional inflammasome upon activation. This suggests a link between microbial activation and fibrosis thereby challenging the current assumption that in SSc, the activation of innate immune responses is exclusively caused by endogenous ligands as a result of tissue damage. Furthermore, the breach of the physical skin barrier of hands/forearms, where the skin is dry and exposed to mechanical stress, with penetration of the basement membrane of the epidermis by microbes or microbial products might even explain the still unsolved mystery of the centripetal progression pattern of skin fibrosis in SSc.

Rolle_Hautmikrobiom.png 

Quelle: Grice EA, et al. Nature Reviews Microbiology 2011; 9:244-253.