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，因为它所表示的细菌是一种医院获得性感染的罪魁祸首，在英国，这种细菌的患病和死亡人数与MRSA不相上下。由Cdiff引起的腹泻病是在抗生素治疗之后发生的，在抗生素治疗中，通常居住在人体肠道中的大量微生物受到了严重干扰。许多其他人类状况很可能是由这种干扰引起或受其影响的。这些通常居住在肠道内的微生物群最近被称为微生物组（存在于特定位置的微生物总数）。确定不同微生物组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，这是不可能通过传统的实验室生长方法，因为许多微生物根本无法培养。基于DNA的分析最近克服了这个问题，但这些主要局限于应用于少数个体样本的小规模研究，因为它们需要大量的财务和计算资源。为了充分认识不同微生物组对人类健康和疾病的影响，我们需要开发一种方法，在涉及许多个体样本的大规模范围内确定和比较它们的组成。我们已经建立了一种经济的高通量方法，将从大量样品集提供微生物组特征。通过这个项目，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。这些方法有可能识别出人类抵抗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验证，这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影响到Cdiff疾病和许多其他传染性和非传染性疾病。

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.