In a recent study published in the Scientific Reports Journal, researchers evaluated the global metabolic profile changes of the skin in relation to the microbiota and ultraviolet (UV) light exposure.
Study: Ultraviolet exposure regulates skin metabolome based on the microbiome. Image Credit: solarseven/Shutterstock.com
Background
Sun exposure, particularly to UV light, is a critical environmental factor influencing human well-being. Ultraviolet radiation can pass through the cutaneous layers to enter the dermis (≤200.0 µm), resulting in molecular changes that alter the local and systemic environments.
The penetrative power of UV light could be exploited to provide therapeutic benefits in cutaneous inflammatory disorders but may also harm the skin, resulting in aging and cancer. In addition, ultraviolet radiation has potent immunosuppressive properties.
Metabolites in skin derived from sebum, sweat, degraded proteins, and interstitial fluid regulate homeostasis, hydration, barrier functions, microbe invasion, immunological responses, and penetration of allergens.
However, the effects of altered lipid and metabolic profiles on the skin are not well-characterized.
Cutaneous microbes are reservoirs of several active biological enzymes involved in molecular metabolism, thereby modulating immunological responses.
The authors of the present study previously demonstrated that the cutaneous microbiota mediates UV radiation effects on the immune responses of the skin.
About the study
In the present study, researchers extended their previous analysis by investigating the alterations in the lipid and metabolic content of the skin in relation to ultraviolet-B (UVB) exposure metabolites and the cutaneous microbiota.
The team exposed six germ-free (GF) murine animals (devoid of the cutaneous microbiome), five disinfected mice (partially devoid of the skin microbiome), and ten control [specific-pathogen-free (SPF)] mice with an intact microbiome to immunosuppressive doses (618.0 mJ/cm2) of UVB radiation.
They performed metabolome and lipidome profiling using murine skin samples by ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS).
In total, targeted data yielded 34.0 targeted metabolites and 111.0 targeted lipid molecules, whereas 502.0 annotated lipid molecules and 3,161.0 unknown features were obtained using untargeted data.
Cutaneous biopsy samples were obtained from the murine animals for lipidomic and metabolomic analyses. The team performed pathway analysis and used the Mummichog automated annotation to provide detailed molecular insights.
In addition, partial least-squares discriminant analysis (PLS-DA) and receiver operating characteristic (ROC) analysis were performed. The shaved dorsal skin of mice was disinfected one day and one hour before UVB exposure.
UV radiation was administered using a light source with an emission range of 280 to 360 nm by positioning the device upside down on the animal cages. The mean values for UVB irradiance of the lamp (mW/cm2) and UVB exposure (minutes) were 2.0 and 5.42, respectively.
Results
UV radiation differentially modulated several metabolites, including choline, alanine, glutamine, histidine, and glycine, in GF mice compared to controls. In addition, membrane lipids such as phosphatidylethanolamine (PE), sphingomyelin, and phosphatidylcholine (PC) were affected by UV exposure, mediated by the cutaneous microbiota.
Before UVB exposure, the metabolic differences between GF mice and controls were largely due to increased PC, PE, phosphatidylserine, and cardiolipins and decreased levels of unknown metabolites.
After UVB exposure, elevated unknown metabolites were key differentiating factors between GF and control mice.
Irrespective of the microbiota, UVB exposure decreased variability from 40% before exposure to 34% after exposure. A similar metabolomic shift was observed in the skin of disinfected mice.
The disinfected skin metabolome also showed significant differences compared to the control mice’s metabolome before and post-UV exposure, largely due to unknown metabolites with elevated glycerophospholipid content.
The lack of microbiota consistently lowered the activities of aspartate, alanine, histidine, and pyrimidine metabolism compared to controls before and post-UVB exposure.
In control mice, UV exposure enhanced the metabolism of amino acids such as tryptophan (Trp), glycine (Gly), serine (Ser), alanine (Ala), aspartic acid (Asp), and asparagine (Asn), whereas reduced metabolism of fatty acids, sphingolipids, and histidine, was observed.
Among germ-free mice, the absence of microbiota and microbe metabolism facilitated the response to UVB, with increased metabolism of vitamin B9 and decreased metabolism of glycosphingolipids and histidine.
Similar findings were observed for disinfected mice, with a significant and strong metabolomic shift, largely due to unknown metabolite molecules with elevated glycerophospholipid content. The shift was considerably stronger among disinfected mice than among GF and control mice.
Disinfecting the skin reduced the metabolism of Asp, Asn, proline (Pro), and arginine (Arg) and lipid-mediated pathways involved in arachidonic acid (ARA) and eicosapentaenoic acid (EPA) metabolism.
In disinfected murine animals, histidine metabolism wasn’t impacted before UV exposure, although similar trends were observed. However, UV radiation significantly reduced histidine-metabolizing activities, similar to GF mice.
The skin metabolome depended strongly on the microbiota, as observed in the germ-free and control animals, and UVB exposure lowered microbiota-driven metabolic differences.
Conclusions
Overall, the study findings showed altered lipid and metabolic profiles of the skin in relation to UVB exposure mediated by the cutaneous microbiota.
The findings indicated that skin microbes contain enzymes that can utilize lipids and alter their concentrations in the skin, potentially contributing to immunomodulatory responses.
The microbiota depletion increased alternate and ascorbate metabolism in UV-exposed GF mice, and the folic acid or vitamin B9 pathway activity was greater among UV-exposed disinfected and GF mice.
Contrastingly, the UV-exposed GF mice showed lower glycosphingolipid metabolism than controls. In the presence of the microbiota, enhanced metabolism of alanine, aspartate, nitrogen, pyrimidine, histidine, and glutamate was observed.
UV exposure enhanced tryptophan metabolism in control mice. Identifying such metabolic alterations could aid in developing new strategies that interfere with particular metabolic pathways to preserve skin health after exposure to UV radiation.
