Development of a high throughput comparative microbiomics platform applied to Clostdridium difficile-associated disease.

Cdiff是一个缩写，最近受到了公众的广泛关注，因为它所指的细菌是导致医院获得性感染的原因，现在在英国的疾病和死亡方面与MRSA不相上下。由Cdiff引起的肠道疾病是抗生素治疗的结果，在抗生素治疗中，通常驻留在人类肠道中的大量微生物受到了严重干扰。很可能许多其他人类状况是由这种扰动引起的或受其影响。这些通常存在于肠道中的微生物集合最近被称为微生物组（存在于特定位置的微生物的总和）。确定不同微生物组的组成是非常可取的，因为这可以使我们能够了解和控制它们影响的条件。然而，这是不可能通过经典的实验室生长方法，因为许多微生物根本无法培养。基于DNA的分析最近已经克服了这个问题，但这些分析主要局限于应用于来自少数个体的样本的小规模研究，因为它们需要巨大的财政和计算资源。为了充分认识不同微生物组对人类健康和疾病的影响，我们需要开发大规模测定和比较其组成的方法，涉及来自许多个体的样本。我们已经建立了一种经济的高通量方法，将提供大量样品集的微生物组学特征。通过该项目，我们的目标是完成开发过程并建立大规模应用于临床样本的方法。在该计划中，我们将对与Cdiff感染相关的微生物组进行初步分析。这些有可能鉴定出人类抵抗Cdiff感染所必需的生物体，因此是一种潜在的保护手段。更确定的结果是验证了一种方法，该方法将成为所有希望进行大规模微生物组学测定和比较的研究人员的资源。这种分析有明显的潜力影响Cdiff疾病和许多其他感染性和非感染性疾病。

Cdiff is an abbreviation that has recently received much public attention as the bacterium it denotes is responsible for a hospital acquired infection that now rivals MRSA in terms of illness and deaths in the UK. The diarrhoeal disease due to Cdiff follows on from antibiotic treatment in which the large number of microbes normally resident in the human gut have been substantially disturbed. It is likely that many other human conditions are either caused by or affected by such disturbances. These collections of microbes normally resident in the gut have recently been referred to as the microbiome (the totality of microbes present at a particular location). It would be highly desirable to determine the composition of different microbiomes as this could enable us to understand and control the conditions that they influence. However, this is not possible by classical laboratory growth methods as many microbes simply cannot be cultured. DNA based analyses have recently surmounted this problem but these are largely confined to small scale studies applied to samples from a few individuals as they demand enormous financial and computing resources. To fully recognize the influence of different microbiomes on human health and disease we need to develop means of determining and comparing their compositions on a large scale involving samples from many individuals. We have established an economic high throughput approach that will provide microbiomic signatures from substantial sample sets. Through this project we aim to complete the development process and establish our approach for large scale application to clinical samples. Within the programme we will make initial analyses of the microbiome associated with Cdiff infection. These have the potential to identify organisms that may be necessary for humans to resist Cdiff infection and therefore a potential means of protection. A more certain outcome is the validation of an approach that will be a resource for all researchers wishing to make large scale microbiomic determinations and comparisons. Such analyses have clear potential to impact on Cdiff disease and many other infective and non-infective conditions.