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

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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.