Phages in the infant gut: a framework for virome development during early life

The human gut is home to trillions of microorganisms including prokaryotes, eukaryotes, and viruses which each have integral roles in maintaining the stability and resilience of this ecosystem, as well as the health of their human host. Bacteriophages (phages) make up the majority of the viral fraction in the gut and are constantly predating on their bacterial hosts [ 1 ]. During the first few years of life, the infant gut microbiota follows a defined successional pattern where both bacterial and phage communities experience consistent shifts in overall abundance and taxonomic composition [ 2 , 3 , 4 , 5 ]. The gradual maturation of gut bacterial communities during early childhood is well described and central to an individual’s healthy development. Perturbations of the gut microbiome early in life, such as antibiotic usage, have been associated with a myriad of health outcomes [ 6 , 7 , 8 ]. In contrast, phage dynamics in the infant gut are not as well characterized, and thus, their potential roles in gut homeostasis and physical and cognitive development remain unclear [ 3 , 9 , 10 ]. Mostly known as agents of bacterial lysis, phages represent an important reservoir of genetic diversity which can confer selective metabolic, immune, and evolutionary advantages to bacterial hosts [ 11 ]. How phages replicate also has distinct consequences on bacterial communities, and by extension the human host [ 11 , 12 , 13 , 14 ]. Assessing the role and contribution of phages to the gut microbial ecosystem is thus necessary to gain insight into the factors shaping microbial succession, better understand the impacts of perturbations, and ultimately to intervene. In this perspective, we first summarize current knowledge on the development of the infant gut microbiome, focusing on phage-bacteria interactions, and speculate on understudied aspects. We then propose a theoretical framework governing the development of the gut virome in early childhood, which is dependent on both phage and bacterial densities and diversity. We conclude by suggesting the use of newly developed single-cell and bioinformatic approaches to decipher the complex network of microbial interactions occurring in the infant gut.