Investigating the role of Lactobacillus Crispatus in healthy skin and psoriasis
Investigating the role of Lactobacillus Crispatus in healthy skin and psoriasis
批准号:
MR/P001394/1
负责人:
Wisam Alwan
金额:
$39.26万
依托单位:
依托单位国家:
英国
项目类别:
Fellowship
财政年份:
2017
资助国家:
英国
项目状态:
已结题
起止时间:
2017 至 --
中文摘要
牛皮癣是一种终生疾病,会导致难看的红色、片状皮肤斑块。它还与其他问题有关,包括肥胖和抑郁症。尽管有一些治疗银屑病的方法,但许多患者目前使用的乳膏和软膏并不能充分控制银屑病。更严重的银屑病可以通过作用于免疫系统的药片和注射来治疗,但这些都与相当大的副作用有关,需要通过多次血液测试和临床就诊进行长期监测。新的基因技术表明,人类皮肤表面存在着各种各样的“无害”细菌。一项对牛皮癣患者和健康志愿者的大型研究表明,这两组人的细菌种类和数量存在差异。皱纹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,这些细菌不是充当“无辜的旁观者”,而是在改变皮肤的免疫系统反应方面发挥重要作用。之前的研究表明,免疫系统的过度活跃在促进银屑病方面起着重要作用。皱纹乳杆菌在健康皮肤中的存在,而不是银屑病,表明它在预防免疫系统过度活动方面可能是重要的。细菌做到这一点的确切方式尚不清楚,但之前的研究已经表明,某些免疫信号通路在防止过度皮肤炎症方面的重要性。我们的研究旨在回答卷曲乳杆菌是否激活了皮肤中这一特定的途径来预防炎症。我们的研究主要包括三个部分:1)通过将卷曲乳杆菌与试管中的细菌混合来测试来自健康志愿者和银屑病患者的皮肤样本(活组织检查)如何受到卷曲乳杆菌的影响2)通过将卷曲乳杆菌与细菌在试管中混合来测试卷曲乳杆菌对银屑病严重程度的影响3)通过将卷曲乳杆菌的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,我将从健康志愿者和银屑病患者的皮肤活检组织中提取它们,并将它们与卷曲乳杆菌的提取物混合。我们还将皮肤细胞(角质形成细胞)从活检组织中分离出来,并用细菌提取物进行治疗。然后我们从细胞和活组织中提取DNA,以测量与牛皮癣有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,我们将使用公认的人类牛皮癣模型。我们用细菌提取物治疗发炎区域,看看这是否改善了牛皮癣的外观和严重程度,并评估了对基因和信使的影响。更多地了解这些细菌在牛皮癣中的作用,可能有助于我们确定未来是否可以在医学上使用它们(例如,以乳膏或软膏的形式)治疗牛皮癣。
英文摘要
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.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.chom.2021.07.007
发表时间:
2021-08
期刊:
Cell host & microbe
影响因子:
30.3
作者:
[W. Alwan;P. Di Meglio]
通讯作者:
W. Alwan;P. Di Meglio
DOI:
10.1016/j.phrs.2023.106848
发表时间:
2023-07
期刊:
Pharmacological research
影响因子:
9.3
作者:
[A. Alangari;M. D. Ashoori;W. Alwan;H. Dawe;B. Stockinger;J. Barker;E. Wincent;P. Di Meglio]
通讯作者:
A. Alangari;M. D. Ashoori;W. Alwan;H. Dawe;B. Stockinger;J. Barker;E. Wincent;P. Di Meglio
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