Bacteriophages: Uncharacterized and Dynamic Regulators of the Immune System

Abstract

The human gut is an extremely active immunological site interfacing with the densest microbial community known to colonize the human body, the gut microbiota. Despite tremendous advances in our comprehension of how the gut microbiota is involved in human health and interacts with the mammalian immune system, most studies are incomplete as they typically do not consider bacteriophages. These bacterial viruses are estimated to be as numerous as their bacterial hosts, with tremendous and mostly uncharacterized genetic diversity. In addition, bacteriophages are not passive members of the gut microbiota, as highlighted by the recent evidence for their active involvement in human health. Yet, how bacteriophages interact with their bacterial hosts and the immune system in the human gut remains poorly described. Here, we aim to fill this gap by providing an overview of bacteriophage communities in the gut during human development, detailing recent findings for their bacterial-mediated effects on the immune response and summarizing the latest evidence for direct interactions between them and the immune system. The dramatic increase in antibiotic-resistant bacterial pathogens has spurred a renewed interest in using bacteriophages for therapy, despite the many unknowns about bacteriophages in the human body. Going forward, more studies encompassing the communities of bacteria, bacteriophages, and the immune system in diverse health and disease settings will provide invaluable insight into this dynamic trio essential for human health.

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

“…Bacteriophages are active regulators of bacterial populations [50][51][52] and changes in phage composition or diversity have been linked to various diseases including Inflammatory Bowel disease, Parkinson's disease and Type 1 Diabetes 53 . Moreover, bacteriophages can protect the epithelium from bacterial infections in a mucus-dependent manner, or can modulate the innate and adaptive arms providing non-host immunity 37,52,[54][55][56][57][58] .…”

Diversity of Microbial Signatures in Asthmatic Airways

“…Such a link has been reported in studies of intestinal inflammatory conditions, such as inflammatory bowel disease; however, to our knowledge, this link has not been tested in allergic respiratory conditions, such as asthma. 70 …”

Phages and Their Role in Gastrointestinal Disease: Focus on Inflammatory Bowel Disease

“…Contrarily, there is also the "Piggyback the Winner" model in which phages may undergo the lytic cycle to take advantage of the rapid reproduction of bacteria. The model presumes that there is a gradient of lysogenic to lytic replication across the mucus layer of the intestine based on the amount of bacterial load in various parts of the mucosal layer [42,43]. Future research will likely uncover which of these hypotheses is closer to the truth.…”