The human body is colonised by a diverse collective of microorganisms, including bacteria, fungi, protozoa and viruses. The smallest entity of this microbial conglomerate are the bacteriophages. Phages colonise all niches of the body, including the skin, oral cavity, lungs, gut and urinary tract. As such our bodies are frequently and continuously exposed to high numbers of phages, and we secrete more than several billion phages per gram of faeces.

Phages cannot infect eukaryotic cells in the same way they infect their bacterial host cells. Nevertheless, phages freely and profusely penetrate our bodies; having been found within the blood, serum, lung, liver, kidney and even within the brain. How phages are capable of crossing confluent epithelial cell barriers and accessing these ‘classically sterile’ regions of the body remained poorly understood.

The Barr Lab proposed bacteriophage transcytosis as a generalised mechanism for phage access to the body, whereby naturally occurring phages are endocytosed and transported across epithelial cell layers. In vitro studies demonstrated the rapid, directional transport of diverse phages across cell lines originating from across the body. Cell biology experiments revealed that phage particles were capable of accessing all endo-membrane components of the eukaryotic cell, with phage transit occurring through the Golgi apparatus before being functionally exocytosed on the contralateral cell membrane.

Based on these results we estimate that the average adult human body transcytoses approximately 31 billion phages from the gut into the body every day. Naturally occurring phages are capable of crossing the confluent epithelial cell layers of the gut, gaining access to the body and result in the accumulation and assembly of an ‘intra-body phageome’.

For more information on this transcytosis mechanism, see “Bacteriophage transcytosis provides a mechanism to cross epithelial cell layers”, or download the PDF here.

For a comprehensive review on bacteriophage biology within the human body, see “A bacteriophages journey through the human body”, or download the PDF here.

Real-time microscopy of mammalian cells (purple border & blue nucleus) internalising bacteriophage particles (green puncta).