Abstract
The skin`s microbiome is predominantly commensalic, harbouring a metabolic potential far exceeding that of its host. While there is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host there is still a lack of models for investigating causality of microbiome-associated pathophysiology or toxicity. We now report on a biologically characterised microbial–skin tissue co-culture that allows studying microbe–host interactions for extended periods of time in situ. The system is based on a commercially available 3D skin model. In a proof-of-concept, this model was colonised with single and mixed cultures of two selected skin commensals. Two different methods were used to quantify the bacteria on the surface of the skin models. While Micrococcus luteus established a stable microbial–skin tissue co-culture, Pseudomonas oleovorans maintained slow continuous growth over the 8-day cultivation period. A detailed skin transcriptome analysis showed bacterial colonisation leading to up to 3318 significant changes. Additionally, FACS, ELISA and Western blot analyses were carried out to analyse secretion of cytokines and growth factors. Changes found in colonised skin varied depending on the bacterial species used and comprised immunomodulatory functions, such as secretion of IL-1α/β, Il-6, antimicrobial peptides and increased gene transcription of IL-10 and TLR2. The colonisation also influenced the secretion of growth factors such as VFGFA and FGF2. Notably, many of these changes have already previously been associated with the presence of skin commensals. Concomitantly, the model gained first insights on the microbiome’s influence on skin xenobiotic metabolism (i.e., CYP1A1, CYP1B1 and CYP2D6) and olfactory receptor expression. The system provides urgently needed experimental access for assessing the toxicological impact of microbiome-associated xenobiotic metabolism in situ.
Highlights
In terms of bacterial numbers and population density our skin comes second to the gut, harbouring more than 200 different bacterial genera with an overall population density between 1 million and 1 billion cells per cm2 (Grice et al 2008, 2009;Ross et al 2019)
Two representative skin commensals were tested for stable colonisation of commercially available 3D skin models in a proof of concept study
The model was tested with two bacterial strains, the Gram-negative P. oleovorans and the Gram-positive M. luteus, both of which were previously isolated from healthy volunteers (Sowada et al 2014)
Summary
In terms of bacterial numbers and population density our skin comes second to the gut, harbouring more than 200 different bacterial genera with an overall population density between 1 million and 1 billion cells per cm (Grice et al 2008, 2009;Ross et al 2019). The picture emerging from these studies shows an intricate relationship between the human host and its microbial colonists, the biological implications of which include commensalic functions such as vitamin and amino acid synthesis or immune modulation as was well as pathophysiologies such as allergies, chronic diseases, behavioural disorders or toxification of xenobiotics (Clemente et al 2012; Platzek et al 1999; Sowada et al 2017; Tralau et al 2015). Albeit less well investigated in terms of potential microbiome interactions many active ingredients are, for example, applied to skin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
