DNA extractions of many human clinical samples can be dominated by human DNA and contain less than 10% bacterial DNA, complicating direct sequence analysis of microbial communities using next-generation sequencing (NGS). Methods that segregate bacterial DNA from the human DNA could facilitate the analysis of microbial communities by NGS in these samples. Here, I propose a method to enrich microbial DNA in human clinical samples by utilizing restriction endonucleases to bind the microbial DNA based DNA motifs only found in bacterial genomes. The restriction endonucleases are bound to magnetic beads and then used to segregate the DNA sample before NGS. This method results in a substantial reduction of human DNA in NGS metagenomes of the bead-bound fraction of clinical samples. There is also an increase in the bacterial taxa known to have a high prevalence of the target sequences in the bound fraction. Based on these results, this method could be used to enrich microbial reads of particular target taxa for NGS outputs in clinical samples and therefore increase coverage of microbial genomes for genome assembly and downstream bioinformatics analyses.
