Ménage à trois in the human gut: interactions between host, bacteria and phages

Key Points The human gut is home to dense bacterial and phage populations that are involved in regulating human health. Phages regulate bacterial abundance, diversity and metabolism in numerous ecosystems, but their effects in the human gut remain largely unexplored. Despite high bacterial abundance and metabolism, the majority of described phages in the gut are integrated within their bacterial hosts, which suggests dynamic interactions that are specific to this system. Different bacteria–phage interactions occur depending on the health status and development stage of the human host. Characterization of these interactions would provide unique ways to improve disease or developmental outcomes. Further research on phage replication cycles and phage pharmacodynamics is essential before considering their therapeutic use for human health. The human gut is host to a dense microbial community that includes a large bacteriophage population. This Review summarizes bacteria and phage dynamics in health and disease, and considers how phages may be harnessed as novel therapeutics to improve disease outcomes. The human gut is host to one of the densest microbial communities known, the gut microbiota, which contains bacteria, archaea, viruses, fungi and other microbial eukaryotes. Bacteriophages in the gut are largely unexplored, despite their potential to regulate bacterial communities and thus human health. In addition to helping us understand gut homeostasis, applying an ecological perspective to the study of bacterial and phage communities in the gut will help us to understand how this microbial system functions. For example, temporal studies of bacteria, phages and host immune cells in the gut during health and disease could provide key information about disease development and inform therapeutic treatments, whereas understanding the regulation of the replication cycles of phages could help harness the gut microbiota to improve disease outcomes. As the most abundant biological entities in our gut, we must consider bacteriophages in our pursuit of personalized medicine.