Microbially competent 3D skin - a novel test system for studying host-microbe interaction

ABSTRACT: The skin`s microbiome is predominantly commensalic, harbouring a metabolic potential far exceeding that of its host. While toxicologically relevant there is still a lack of suitable models.  We now report on a new biologically characterised 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 M. luteus established a stable co-culture, P. 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 were varied dependent 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 many grows factors 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 the microbiome’s xenobiotic metabolism in situ.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129864 | GEO | 2021/04/01

REPOSITORIES: GEO