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

微生物群在皮肤对紫外线辐射反应中的作用？

• 批准号: BB/V007734/1
• 负责人: Catherine O'Neill
• 金额: $ 81.76万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV007734%2F1
• 关键词: role; microbiota; response; skin; ultraviolet

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.

现在很清楚，我们的健康在很大程度上取决于存在于我们体内和体外的微生物，即微生物组。皮肤也不例外，我们现在知道，生活在我们皮肤上的细菌为我们提供了许多基本功能，例如对抗感染和帮助增强皮肤作为屏障的作用。皮肤及其微生物组是独特的，因为它们经常暴露在阳光下。长期以来，人们都知道阳光会破坏皮肤细胞的DNA。DNA损伤与“晒伤”有关，这可能是皮肤对阳光最常见的反应，沿着晒黑。然而，即使暴露在阳光下不会导致晒伤，也足以损伤DNA，但通常情况下，皮肤细胞能够非常迅速地修复这种损伤。然而，任何严重到无法修复的损伤都是通过细胞经历一个称为“凋亡”的过程来处理的，这是一种非常可控的细胞死亡方式。这个过程对于阻止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组尚不清楚。然而，我们已经证明，在我们的皮肤上有一种特殊的细菌，它会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响应阳光，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我们的皮肤细胞在阳光照射后的工作方式。在本项目中，我们将对此进行更多调查。我们的第一个问题是：“微生物组的存在会影响人类的晒伤反应吗？”'.我们将通过从10名志愿者的皮肤区域去除微生物组（通过用酒精清洁），然后将他们暴露在几个剂量的“模拟阳光”下来回答这个问题。我们将研究在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。我们将采取“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一个基本问题，即皮肤微生物组在人类晒伤反应中的作用。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，我们有数据显示其在分离的皮肤细胞中的作用。我们现在要看的是真实的皮肤。我们能够从选择性整形外科手术中获得皮肤，并且我们已经建立了在实验室中保持这种皮肤“活着”的方法。我们将用它来研究这种分子在真实的人体皮肤中的作用。我们的目标还在于从细菌中纯化分子，并试图识别它是什么。我们还将研究这种分子如何导致皮肤细胞凋亡。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：“皮肤微生物组中是否有其他细菌可以保护皮肤免受阳光照射后的DNA损伤或促进DNA修复？'.我们已经（在以前的项目中）从健康人体中分离出150多种细菌。我们将对这些细菌进行测试，以确定它们中是否有任何一种可以减少DNA损伤或加速受损DNA的修复。这项工作的成功完成将确定可用作新型防晒霜或“晒后”皮肤护理的细菌。该项目受益于Walgreen Boots Alliance（又名“Boots the Chemist”）和Croda PLC（特种化学品制造的全球领导者）作为项目合作伙伴。更好地了解微生物组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新的方法来帮助消费者保护皮肤。