The relationship between the phageome and human health: are bacteriophages beneficial or harmful microbes?

In the context of the global antibiotic resistance crisis, bacteriophages are increasingly becoming promising antimicrobial agents against multi-resistant bacteria. Indeed, a huge effort is being made to bring phage-derived products to the market, a process that will also require revising the current regulations in order to facilitate their approval. However, despite the evidence supporting the safety of phages for humans, the general public would still be reluctant to use 'viruses' for therapeutic purposes. In this scenario, we consider that it is important to discuss the role of these microorganisms in the equilibrium of the microbiota and how this relates to human health. To do that, this review starts by examining the role of phages as key players in bacterial communities (including those that naturally inhabit the human body), modulating the species composition and contributing to maintain a 'healthy' . Additionally, in specific situations, e.g. an infectious disease, bacteriophages can be used as target-specific antimicrobials against pathogenic bacteria (phage therapy), while being harmless to the desirable microbiota. Apart from that, incipient research shows the potential application of these viruses to treat diseases caused by bacterial dysbiosis. This latter application would be comparable to the use of probiotics or prebiotics, since bacteriophages can indirectly improve the growth of beneficial bacteria in the gastrointestinal tract by removing undesirable competitors. On the other hand, possible adverse effects do not appear to be an impediment to promote phage therapy. Nonetheless, it is important to remember their potentially negative impact, mainly concerning their immunogenicity or their potential spread of virulence and antibiotic resistance genes, especially by temperate phages. Overall, we believe that phages should be largely considered beneficial microbes, although it is paramount not to overlook their potential risks.