Mining the microbes – the human microbiome as model

Abstract

While the number of completed microbial genomes is steadily increasing, a further explosion of genomic sequencing has been developing with the deployment of post‐Sanger sequencing instruments that couple amazing technology and extreme throughput with fancy and imaginative names (Mardis, 2008). Assuming that ABC issues on the accuracy, bioinformatics and costs are solved, the impact of this next‐generation sequencing technology on the future developments in microbial biotechnology may well be beyond our present imagination. What can be envisaged now is already quite wild and includes many technological applications for (meta)genome discovery, SNP analysis and transcriptome profiling. These can be implemented in all phases of discovery, optimization and quality control, while being applicable to all colours of the biotechnology rainbow, ranging from red to green and white to blue. However, the most exciting applications that are specific for the microbial world still have to come and relate to the mining of the global microbial diversity and function. This requires more than only metagenome sequencing as can be illustrated for the largest microbial ecosystem that is closest to our heart: our microbes inside. Intestinal microbes dominate our body since birth and outnumber our own cells by one or more orders of magnitude (Zoetendal et al., 2008). There are a variety of well‐funded metagenome sequencing projects in all corners of the world that aim to characterize the role of these intestinal microbes in health and disease (see Mullard, 2008). These projects on the microbiome of the human intestine and other body parts have recently been united in a large global initiative, the International Human Microbiome Consortium that is providing a platform for data sharing between the US National Institutes of Health and the European Commission (see URL: http://cordis.europa.eu/search/index.cfm?fuseaction=news.document&N_RCN=30004). This platform may also provide a means to generate the needed coordination on data quality and protocols that are highly relevant with the implementation of next‐generation sequencing technologies. What will be the outcome of this massive sequencing operation? Exposing the function of specific microbes and their genes will be obvious targets, in the line with recent examples of intestinal microbes (Konstantinov et al., 2008; Sokol et al., 2008). However, this will require a long process of functional discovery that can be initiated by the microbiome sequencing effort but also requires growth and isolation of the intestinal microbes that are fastidious, anaerobic or require cell–cell contact for growth. Significant progress has been made here with the development of throughput culturing devices (Ingham et al., 2007). However, there is ample room for improvement, notably at the level of microbial interactions and varying growth conditions. A shorter time horizon can be foreseen for microbiome‐based microbial diagnostics that will allow rapid insight in intestinal microbial diversity. Specific high‐throughput systems are already in place (Zoetendal et al., 2008) and can be expanded to be of use for nutritional and pharmaceutical interventions as well as to discriminate between health and disease state of the intestinal tract. Given the abundance and vast coding capacity of the intestinal microbiome, it will be of great interest to follow the developments in the International Human Microbiome Consortium and see whether it can serve as a model for other ecosystems where next‐generation sequence technology is applied to expose the coding capacity and function of the microbial world on our planet.