Multi-omic analysis to evaluate solar exposure impact on skin ecosystem and a new SPF50+ photoprotective system
Podium 51
Presented by: Carine Jacques
As the skin is the primary interface with the external environment, the skin ecosystem consisting of our microbiota, a collection of micro-organisms such as bacteria, viruses, and fungi reflect the state of the surrounding skin ecosystem. To evaluate the impact of external factors like sun exposure, the cutaneous ecosystem, that are skin, hydrolipidic film and microbiome, has to be studied as a whole to understand how they interact with each other and contribute to reply to external stress like sun exposure. Its impact in gut health and disease is widely accepted, but we are just starting to understand the role of cutaneous microbiota and its interaction with skin.
When chronically exposed to sun radiation, Skin not only results in medical conditions like sunburn and cancer, but also influences its phenotypic appearance inducing photo aging. Therefore, sun avoidance and the use of sunscreens to prevent these effects of major public health issue. The consequences of sun exposure have been previously documented both at genetic and proteomic levels. However, only few studies describe the contribution of sun exposure to biochemical changes that result in skin metabolome alterations, and interactions between skin and its microbiota have not been described.
Metabolomics is the most recent systems biology omics approach. It measures the abundance of various metabolites, thus profiling different metabolic pathways. The metabolome is composed of all the low molecular weight compounds of endogenous nature, which are important substrates, by-products, and building blocks of many different biological processes but also of exogenous compounds and their biotransformation by the body. These high-throughput technologies generate high-resolution and high-quality data on the physiological and metabolic state of a target tissue. However, to date, there are very few studies of dermatological outcomes combining multiple omics measurements within the same experiment, in particular metabolomics, lipidomics, metagenomics.
We developed a reconstructed human epidermal model colonized with skin microbiota and sebum (18 donors) to reproduce the complexity of the skin ecosystem. This model gets closer to the reality of the cutaneous physiology and permits to study the interactions between skin and microbiota. The in vitro model, we developed, was exposed to simulated solar radiation (SSR) using a Suntest CPS+ chamber equipped with an NXE 1500 Xenon lamp. A new SPF50+ photoprotective system containing a specific combination of four sun filters (TriAsorB, Tinosorb S, Uvinul T150 and Uvinul A+) and affording a broad spectrum UVB+A photoprotection (patented association WO581; WO984), was evaluated on this in vitro model.
Metabolomics profiles were performed with nuclear magnetic resonance (NMR) and Ultra High-Pressure Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS). Data were processed with XCMS using W4M and filtered using quality control samples. Identified discriminant metabolites according to in-house databases were mapped on metabolic pathways using the software Metexplore.
Metagenomics analyses were performed from genomic DNA extract samples. Intergenic spacers 1 (ITS1) of the ribosomal RNA gene, or of the V1-V3 region of 16S gene was sequenced by high-speed sequencing. Analysis of the sequences by comparison with international data bases and differential analysis was used to identify genus or species more abundant in one group than the other.
Several pathways were modulated after sun exposition. We found that the skin is under high oxidative stress with modification of glutathione and purine pathway but also urea cycle. As already described in vivo by Randhawa et al, the skin goes to catabolism rather than anabolism pathway, and produces higher oxidative stress. Other pathways have been highlighted, in particular linked to skin microbiota, like BCAAs cycle, lipid metabolism and tryptophan pathway, showing interactions between skin and its microbiota. When the new photoprotective system is applied on in vitro model, metabolome of the skin was preserved and the interactions between skin and its ecosystem were protected from sun exposure deleterious effects.
Here, we present the first study which profiled a wide range of metabolites and identified a highly accurate metabolomic signature of sun exposed skin in an in vitro model with complete skin ecosystem. Metabolomic signature can be correlated to the metagenomic analysis of skin microbiota and explain interactions between skin and cutaneous microbiota.
Our original in vitro model coupled with innovative technologies enable evaluation of photoprotection products and understand skin ecosystem interaction.
When chronically exposed to sun radiation, Skin not only results in medical conditions like sunburn and cancer, but also influences its phenotypic appearance inducing photo aging. Therefore, sun avoidance and the use of sunscreens to prevent these effects of major public health issue. The consequences of sun exposure have been previously documented both at genetic and proteomic levels. However, only few studies describe the contribution of sun exposure to biochemical changes that result in skin metabolome alterations, and interactions between skin and its microbiota have not been described.
Metabolomics is the most recent systems biology omics approach. It measures the abundance of various metabolites, thus profiling different metabolic pathways. The metabolome is composed of all the low molecular weight compounds of endogenous nature, which are important substrates, by-products, and building blocks of many different biological processes but also of exogenous compounds and their biotransformation by the body. These high-throughput technologies generate high-resolution and high-quality data on the physiological and metabolic state of a target tissue. However, to date, there are very few studies of dermatological outcomes combining multiple omics measurements within the same experiment, in particular metabolomics, lipidomics, metagenomics.
We developed a reconstructed human epidermal model colonized with skin microbiota and sebum (18 donors) to reproduce the complexity of the skin ecosystem. This model gets closer to the reality of the cutaneous physiology and permits to study the interactions between skin and microbiota. The in vitro model, we developed, was exposed to simulated solar radiation (SSR) using a Suntest CPS+ chamber equipped with an NXE 1500 Xenon lamp. A new SPF50+ photoprotective system containing a specific combination of four sun filters (TriAsorB, Tinosorb S, Uvinul T150 and Uvinul A+) and affording a broad spectrum UVB+A photoprotection (patented association WO581; WO984), was evaluated on this in vitro model.
Metabolomics profiles were performed with nuclear magnetic resonance (NMR) and Ultra High-Pressure Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS). Data were processed with XCMS using W4M and filtered using quality control samples. Identified discriminant metabolites according to in-house databases were mapped on metabolic pathways using the software Metexplore.
Metagenomics analyses were performed from genomic DNA extract samples. Intergenic spacers 1 (ITS1) of the ribosomal RNA gene, or of the V1-V3 region of 16S gene was sequenced by high-speed sequencing. Analysis of the sequences by comparison with international data bases and differential analysis was used to identify genus or species more abundant in one group than the other.
Several pathways were modulated after sun exposition. We found that the skin is under high oxidative stress with modification of glutathione and purine pathway but also urea cycle. As already described in vivo by Randhawa et al, the skin goes to catabolism rather than anabolism pathway, and produces higher oxidative stress. Other pathways have been highlighted, in particular linked to skin microbiota, like BCAAs cycle, lipid metabolism and tryptophan pathway, showing interactions between skin and its microbiota. When the new photoprotective system is applied on in vitro model, metabolome of the skin was preserved and the interactions between skin and its ecosystem were protected from sun exposure deleterious effects.
Here, we present the first study which profiled a wide range of metabolites and identified a highly accurate metabolomic signature of sun exposed skin in an in vitro model with complete skin ecosystem. Metabolomic signature can be correlated to the metagenomic analysis of skin microbiota and explain interactions between skin and cutaneous microbiota.
Our original in vitro model coupled with innovative technologies enable evaluation of photoprotection products and understand skin ecosystem interaction.