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

Cdiff是一个缩写，最近受到了公众的极大关注，因为它所指的细菌是医院获得性感染的罪魁祸首，现在英国的疾病和死亡人数与MRSA不相上下。由Cdiff引起的腹泻疾病是在抗生素治疗之后发生的，在抗生素治疗中，通常驻留在人体肠道中的大量微生物受到了实质性的干扰。很可能，许多其他人类状况要么是由这种干扰造成的，要么是受其影响的。这些通常驻留在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数)。确定不同微生物群的组成将是非常可取的，因为这可以使我们了解和控制它们影响的条件。然而，传统的实验室培养方法不可能做到这一点，因为许多微生物根本无法培养。基于DNA的分析最近克服了这个问题，但这些分析在很大程度上局限于对几个人的样本进行的小规模研究，因为它们需要巨大的财政和计算资源。为了充分认识到不同微生物群对人类健康和疾病的影响，我们需要开发一种手段，在大范围内确定和比较它们的组成，包括来自许多个人的样本。我们已经建立了一种经济的高通量方法，将从大量样本集提供微生物签名。通过这个项目，我们的目标是完成开发过程，并建立我们的方法，大规模应用于临床样本。在该方案中，我们将对与Cdiff感染有关的微生物群进行初步分析。这些方法有可能识别人类抵抗Cdiff感染所必需的生物体，从而成为一种潜在的保护手段。一个更确定的结果是一种方法的有效性，该方法将成为所有希望进行大规模微生物组测定和比较的研究人员的资源。这种分析显然有可能对Cdiff病和许多其他感染性和非感染性疾病产生影响。

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.