Metagenomic epidemiology: a public health need for the control of antimicrobial resistance.

The intestine is an 'environment', a shared space where the interior and the exterior of the organism merge. The complexity of the intestinal microbiome modulates such interaction, and reflects the coordinated evolution of animals and intestinal microbes. The intestinal microbiome is exposed to the environmental resistome, to intestinal organisms from other hosts and also to microbiome-damaging agents, such as antibiotics. The result is a 'genetic-genomic-metagenomic reactor' where resistance genes flow among different biological units of different hierarchical levels, such as integrons, transposons, plasmids, clones, species or genetic exchange communities. Metagenomics provides the possibility to explore the presence of antibiotic resistance genes in all these biological and evolutionary units, and to identify possible 'high risk associations'. Multi-layered metagenomic epidemiology is required to understand and eventually to predict and apply interventions aiming to limit antibiotic resistance.