The immense diversity of the human gut microbiome is known to be important for normal physiology and host immune defense. It is thought that genomes of this complex ecological community encode for 3.3 million genes.4 However, the relationship between human health and disease and the composition of the gut microbiota is not fully understood.2,3 In 2008, the Human Microbiome Project was initiated with the goal of sequencing over 1000 genomes and characterizing the complex microbial communities of several body sites.1 Efficient computational analysis of the sequence data, functional genomic data and metadata required a novel analytical tool to isolate important information.1 Here we use a parametric method, which relies on species-specific nucleotide signatures, to detect horizontal gene transfer (HGT) events among microbiota of the human gut. To accurately identify candidate proteins, we combined the parametric method utilizing GC content and the DarkHorse algorithm utilizing phylogenetic methods to account for intra-genomic variation and to prove the validity of the candidate protein based on its historical profile of HGT events. Further analysis of the catalytic function and metabolic processes performed by these proteins will improve our understanding of the dynamic relationship between the gut microbiome and human health. We showed that the human gut facilitates horizontal gene transfer of antibiotic resistant genes and genes important for virulence. These results suggest that these microbes have converged on similar functions that are important for normal physiological state of the host. An understanding of the role these genes play in metabolism and other biological functions will help elucidate the molecular mechanism by which these microbiota influence immunological, metabolic and neurological disease pathology.