Investigating the role of Lactobacillus Crispatus in healthy skin and psoriasis

牛皮癣是一种终身的疾病，会导致难看的红色，皮肤斑块。它还与其他问题有关，包括肥胖和抑郁症。虽然存在一些治疗牛皮癣的方法，但许多患者使用目前可用的乳膏和软膏无法充分控制。更严重的牛皮癣是用作用于免疫系统的片剂和注射剂治疗的，但这些都与相当大的副作用有关，需要长期监测，许多血液检查和诊所就诊。新的基因技术已经显示了居住在人类皮肤表面的各种“无害”细菌。一项针对银屑病患者和健康志愿者的大型研究表明，两组之间的细菌类型和数量存在差异。卷曲乳杆菌是一种在皮肤上发现的细菌，在健康皮肤中比牛皮癣更常见。这一发现的意义尚不清楚。然而，有证据表明，这些细菌可能在改变皮肤免疫系统反应方面发挥重要作用，而不是充当“无辜的旁观者”。以前的研究表明，免疫系统的过度活跃在促进牛皮癣中很重要。卷曲乳杆菌存在于健康皮肤中，而不是牛皮癣，这表明它可能对预防免疫系统过度活跃很重要。细菌这样做的确切方式尚不清楚，但以前的研究表明某些免疫信号通路在预防过度皮肤炎症中的重要性。我们的研究旨在回答卷曲乳杆菌是否会激活皮肤中的这一特定途径来预防炎症。我们的研究主要包括三个部分：1）测试皮肤样本如何健康志愿者和银屑病患者的（活组织检查）通过将卷曲乳杆菌与试管中的细菌混合而受到卷曲乳杆菌的影响2）通过将卷曲乳杆菌与试管中的细菌混合来测试健康志愿者和银屑病患者的皮肤细胞如何受到卷曲乳杆菌的影响3）通过将细菌提取物应用于银屑病模型来测试卷曲乳杆菌对银屑病严重程度的影响为了回答这个问题，我将采取从健康志愿者和银屑病患者的皮肤活检组织中取出，并将它们与卷曲乳杆菌的提取物混合。我们还从活检中分离皮肤细胞（角质形成细胞），并用细菌提取物处理这些细胞。然后，我们从细胞和活检中提取DNA，以测量与银屑病相关的基因和化学信使的水平。为了进一步了解细菌对生命系统的影响，我们将使用完善的人类银屑病模型。我们用细菌提取物治疗发炎部位，看看这是否能改善银屑病的外观和严重程度，并评估对基因和信使的影响。更多地了解这些细菌在银屑病中的作用可能有助于我们确定将来是否可以在医学上使用它们（例如以乳膏或软膏的形式）来治疗银屑病。

Psoriasis is a life-long condition that causes unsightly red, flaky patches of skin. It is also linked with other problems including obesity and depression. Although some treatments exist for psoriasis, many patients do not have adequate control with currently available creams and ointments. More severe psoriasis is treated with tablets and injections that act on the immune system, but these are associated with considerable side effects and require long term monitoring with many blood tests and clinic visits. New genetic techniques have shown a diverse collection of 'harmless' bacteria that reside on the surface of human skin. A large study of patients with psoriasis and healthy volunteers have shown that there is are differences in the types and numbers of bacteria between the two groups. Lactobacillus Crispatus is a type of bacteria found on the skin that is more common in healthy skin than psoriasis.The meaning of this finding is not yet clear. However there is evidence that rather than acting as 'innocent bystanders', these bacteria may have an important role in altering the immune system response in the skin. Previous research has shown that overactivity of the immune system is important in promoting psoriasis. The presence of Lactobacillus Crispatus in healthy skin but not psoriasis suggests it may be important in preventing overactivity of the immune system. The exact way that the bacteria do this is not known, but previous studies have shown the importance of certain immune signaling pathways in preventing excess skin inflammation. Our study looks to answer if Lactobacillus Crispatus activates this particular pathway in the skin to prevent inflammation.There are three main parts to our study:1) Test how skin samples (biopsies) from healthy volunteers and psoriasis patients are affected by Lactobacillus Crispatus by mixing them with the bacterium in test tubes2) Test how skin cells from healthy volunteers and psoriasis patients are affected by Lactobacillus Crispatus by mixing them with the bacterium in test tubes3) Test the effects of Lactobacillus Crispatus on psoriasis severity by applying extracts of the bacterium to a model of psoriasisTo answer this I will take skin biopsies from healthy volunteers and psoriasis patients and mix them with extracts of Lactobacillus Crispatus. We also separate skin cells (keratinocytes) from biopsies and treat these with extracts of the bacterium. We then remove DNA from the cells and biopsies to measure the levels of genes and chemical messengers linked to psoriasis.To further understand the effects that bacteria have on live systems, we will use well established models of human psoriasis. We treat the inflamed area with extracts of the bacterium to see if this improves the appearance and severity of psoriasis and also asses the effect on genes and messengers. Learning more about the role of these bacteria in psoriasis may help us identify if we can use them medically (for example in the form of creams or ointments) to treat psoriasis in the future.