Human Phageprints: A high-resolution exploration of oral phages reveals globally-distributed phage families with individual-specific and temporally-stable community compositions

Metagenomic studies have revolutionized the study of novel phages. However these studies trade the depth of coverage for breadth. In this study we show that the targeted sequencing of a phage genomic region as small as 200-300 base pairs, can provide sufficient sequence diversity to serve as an individual-specific barcode or Phageprint. The targeted approach reveals a high-resolution view of phage communities that is not available through metagenomic datasets. By creating instructional videos and collection kits, we enabled citizen scientists to gather ~700 oral samples spanning ~100 individuals residing in different parts of the world. In examining phage communities at 6 different oral sites, and by comparing phage communities of individuals living across the globe, we were able to study the effect of spatial separation, ranging from several millimeters to thousands of kilometers. We found that the spatial separation of just a few centimeters (the distance between two oral sites) can already result in highly distinct phage community compositions. For larger distances, spanning the phage communities of different individuals living in different parts of the world, we did not observe any correlation between spatial distance and phage community composition as individuals residing in the same city did not have any more similar phage communities than individuals living on different continents. Additionally, we found that neither genetics nor cohabitation seem to play a role in the relatedness of phage community compositions across individuals. Cohabitating siblings and even identical twins did not have phage community compositions that were any more similar than those of unrelated individuals. The primary factor contributing to phage community composition relatedness is direct contact between two habitats, as is demonstrated by the similarity between oral phage community compositions of partners. Furthermore, by exploring phage communities across the span of a month, and in some cases several years, we observed highly stable community compositions. These studies consistently point to the existence of remarkably diverse and personal phage families that are stable in time and apparently present in people around the world.