A role for the microbiota in the response of skin to ultraviolet radiation?

现在很清楚，我们的健康很大程度上取决于存在于我们体内和体表的微生物，即微生物群。皮肤也不例外，我们现在知道，生活在皮肤上的细菌为我们提供了许多基本功能，如抵抗感染和帮助增强皮肤作为屏障的作用。皮肤及其微生物群的独特之处在于它们经常暴露在阳光下。很长一段时间以来，人们都知道阳光会损害皮肤细胞的DNA。DNA损伤与“晒伤”有关，晒伤和晒黑可能是皮肤对阳光最广为人知的反应。然而，即使没有晒伤的暴露也足以损伤DNA，但通常情况下，皮肤细胞能够很快修复这种损伤。然而，任何严重到无法修复的损伤都是由细胞通过一种叫做“细胞凋亡”的过程来处理的，这是一种非常受控制的细胞死亡方式。这一过程对于阻止DNA受损的细胞增殖至关重要，也是皮肤防御肿瘤形成的一部分。暴露在阳光下如何影响我们的皮肤微生物群还不清楚。然而，我们已经证明，我们的皮肤上有一种特殊的细菌，可以促进暴露在阳光下的皮肤细胞的凋亡。这种细菌通过产生一种分子来对阳光做出反应，这种分子会诱导皮肤细胞凋亡。这表明，我们的皮肤微生物组产生的分子会改变皮肤细胞在阳光照射后的工作方式。在这个项目中，我们将对此进行更多的研究。我们的第一个问题是：“微生物群的存在会影响人类对晒伤的反应吗？”为了回答这个问题，我们将从10名志愿者的皮肤区域去除微生物（用酒精清洁），然后将他们暴露在几剂量的“模拟阳光”下。我们将研究没有微生物组的皮肤区域与有微生物组的皮肤区域相比，晒伤是如何发展的。我们将对他们的皮肤进行“活组织检查”——一小块暴露在阳光下的皮肤，我们将在实验室进行实验，以确定这片皮肤中的细胞是否发生了凋亡。这项工作的成功完成将回答皮肤微生物组在人类晒伤反应中的作用这一基本问题。我们的第二个问题与细菌产生的促进细胞凋亡的分子有关。目前我们有关于它在分离的皮肤细胞中的作用的数据。我们现在想看看真正的皮肤。我们可以通过选择性整形手术获得皮肤，并且我们已经建立了在实验室中保持皮肤“存活”的方法。我们将用它来研究这种分子在真实人体皮肤中的作用。我们还致力于从细菌中纯化分子，并试图确定它是什么。我们还将研究这种分子是如何导致皮肤细胞凋亡的。这项工作的成功完成将揭示细菌在保护皮肤免受受损皮肤细胞增殖方面的可能作用。我们的最后一个问题是：“皮肤微生物群中是否有其他细菌可以保护DNA免受阳光照射后的损伤或促进DNA修复？”我们已经（在之前的一个项目中）从健康人身上分离出了150多种细菌。我们将对这些细菌进行测试，看看它们是否能减少DNA损伤或加速受损DNA的修复。这项工作的成功完成将鉴定出可用于新型防晒霜或“晒后”皮肤治疗的细菌。该项目得益于沃尔格林博姿联盟（又名“博姿化学家”）和Croda PLC（特种化学品制造的全球领导者）作为项目合作伙伴。更好地了解微生物群保护皮肤免受阳光照射的方式，将有助于这些项目合作伙伴开发帮助消费者保护皮肤的新方法。

It is now clear that our health depends largely on the microbes that exist in and on our bodies i.e. the microbiome. Skin is no exception and we now know that bacteria living on our skin provide us with many essential functions such as combatting infections and helping to enhance the role of skin as a barrier.The skin and its microbiome are unique in that they are regularly exposed to sunlight. For a long time it has been known that sunlight can damage the DNA of skin cells. DNA damage is associated with 'sunburn' which is perhaps, along with tanning, the most well known response of skin to sunlight. However, even exposure which does not cause a sunburn can be sufficient to damage DNA but usually, the skin cells are able to repair this damage very quickly. However, any damage that is too bad to repair is dealt with by the cells undergoing a process called 'apoptosis' which is a very controlled way of the cells dying. This process is essential to stop cells with damaged DNA from multiplying and is part of the skin's defence against forming tumours. How exposure to sunlight affects our skin microbiome is not really known. However, we have shown that there is a particular bacterium on our skin which promotes apoptosis in skin cells that have been exposed to sunlight. This bacterium does this by producing a molecule in response to sunlight that induces apoptosis in skin cells. This shows that our skin microbiome produces molecules that alter how our skin cells work following sunlight exposure. In this project we will be investigating this more. Our first question is: 'Does the presence of the microbiome affect the sunburn response in humans?'. We will answer this by removing the microbiome (by cleaning with alcohol) from an area of skin in 10 volunteers and then exposing them to several doses of 'simulated sunlight'. We will be looking at how the sunburn develops in areas of skin without the microbiome compared to with the microbiome. We will take a 'biopsy' - a small piece of their skin which has been sunlight exposed and we will perform experiments in the laboratory to determine whether cells in this piece of skin have undergone apoptosis. Successful completion of this work will answer a fundamental question as to the role of the skin microbiome in the sunburn response in humans.Our second question relates to the molecule produced by the bacterium that promotes apoptosis. At present we have data as to its effects in isolated skin cells. We now want to look at this in actual skin. We are able to obtain skin from elective plastic surgery procedures and we have methods already established to keep this skin 'alive' in the laboratory. We will be using this to investigate the effects of the molecule in real human skin. We also aim to purify the molecule from the bacterium and try to identify what it is. We will also be studying how the molecule causes apoptosis in skin cells.Successful completion of this work will shed light on the possible role of bacteria in protecting skin against the multiplication of damaged skin cells.Our final question is: 'Are there other bacteria in the skin microbiome that can protect against DNA damage following exposure to sunlight or promote DNA repair?'. We have already (in a previous project) isolated over 150 types of bacteria from healthy humans. We will be testing these bacteria to find out whether any of them can reduce DNA damage or speed up repair of damaged DNA.Successful completion of this work will identify bacteria that could be used as novel sunscreens or 'after sun' treatments for skin. This project benefits from having Walgreen Boots Alliance (aka 'Boots the Chemist') and Croda PLC (a global leader in the manufacture of speciality chemicals) as project partners. A better understanding of the ways in which the microbiome protects skin against sunlight will be beneficial in helping these project partners develop new ways to help consumers protect their skin.