Microbial genomics: an increasingly revealing interface in human health and disease

Abstract

Th e diverse microbial communities associated with humans are now beginning to be comprehensively interro gated and characterized, thanks to new genomic, metagenomic and other high-throughput approaches. However, there is a huge amount of work to be done that will require a large-scale eff ort from the scientifi c commu nity, particularly in the development and application of analysis tools and in achieving a biological understanding of the human-microbe interface. Th is endeavor has already begun with projects such as MetaHIT [1] and the Human Microbiome Project Consortium [2] taking advantage of the extensive advances made with the advent of highly parallel next-generation sequencing approaches. But I would call for one additional eff ort: in the midst of all the thousands of microbial genomes, the role of one additional genome the human genome - should also be fully evaluated. It is becoming increasingly clear that human genetic variants, particularly in microbial sensing genes, might infl uence the structure of the human-associated microbial communities and lead to diseases such as infl ammatory bowel disease [3]. Interestingly, the shaping of these microbial communities, infl uenced by the human genome, might occur during the early colonization following birth and might infl uence many of the subsequent microbiome interactions. Genome-scale methods allow us to move away from targeted investigations, which are necessarily limited to our knowledge of candidate genes, to population-based analyses that permit the full genomic repertoire to be interrogated, enabling the discovery of key mutations and mechanisms that drive host-microbe (and microbemicrobe) interactions in their natural environment. However, even when all the genes in a genome have been identifi ed, detailed studies at the molecular level are required to provide novel mechanistic insights. Without such understanding, the statistical associations between microbial genes and their products that are currently being linked to medical outcomes may not stand fi In this issue, we launch a new article series highlighting the application of genomic and other high-throughput approaches to investigate the role of microbes in human health and disease. Forthcoming articles will feature recent progress in characterizing, detecting, monitoring and understanding the underlying mechanisms involved in infectious diseases, the role of the microbiome, and how such information can be applied to medicine. Th ere is great potential in this fifrom basic and technological advances to their application and integration into clinical approaches for disease prediction, surveillance, diagnosis and treatment.