The human body is completely porous to bacteriophages. Phages–short for bacteriophages– cannot infect Eukaryotic cells as the cell-surface receptors and intracellular machinery are too different from their bacterial hosts. Nevertheless, phages freely and profusely penetrate our bodies as well as the bodies of other higher vertebrates. In fact the complete penetration of the body by bacteriophages has been known for over 50 years. Phages have been detected in the blood and serum of both symptomatic and asymptomatic humans. Phage migration to the blood was rapidly followed by their permeation into all major organs of the body, including the lung, liver, kidney, spleen, urinary tract and even the brain, indicating their capacity to cross the blood-brain barrier.
Although the ingress of these phages throughout the body has been previously described, few attempts have been made to investigate whether phage transcytosis occurs naturally and, consequently the principal route that phages use to access the body has yet to be identified. Here, we report a generalised mechanism whereby phages are transported into and across epithelial cell layers. In vitro studies demonstrate the rapid and directional transcytosis of diverse phages across cell lines originating from the gut, lung, liver, kidney and brain. Approximately 0.1% of free bacteriophage particles were functionally transcytosed by confluent epithelial cells. Fluorescence microscopy and cell fractionations revealed that phage particles appeared to transit through the Golgi apparatus and were capable of accessing all microsomal compartments of the eukaryotic cell. Based on this experimental data, we estimate that thirty-one billion bacteriophage particles are transcytosed by the average human body each day. The transcytosis of bacteriophage into the body is a natural and ubiquitous process that may have important implications for vertical transmission, immune-stimulatory effects on the body and the utilisation of a third external genome.