Biogeography and Environmental Conditions Shape Phage and Bacteria Interaction Networks Across the Healthy Human Microbiome
Viruses and bacteria are critical components of the human microbiome and play important roles in health and disease. Most previous work has relied on studying microbes and viruses independently, thereby reducing them to two separate communities. Such approaches are unable to capture how these microbial communities interact, such as through processes that maintain community stability or allow phage-host populations to co-evolve. We developed and implemented a network-based analytical approach to describe phage-bacteria network diversity throughout the human body. We accomplished this by building a machine learning algorithm to predict which phages could infect which bacteria in a given microbiome. This algorithm was applied to paired viral and bacterial metagenomic sequence sets from three previously published human cohorts. We organized the predicted interactions into networks that allowed us to evaluate phage-bacteria connectedness across the human body. We found that gut and skin network structures were person-specific and not conserved among cohabitating family members. High-fat diets and obesity were associated with less connected networks. Network structure differed between skin sites, with those exposed to the external environment being less connected and more prone to instability. This study quantified and contrasted the diversity of virome-microbiome networks across the human body and illustrated how environmental factors may influence phage-bacteria interactive dynamics. This work provides a baseline for future studies to better understand system perturbations, such as disease states, through ecological networks.
The human microbiome, the collection of microbial communities that colonize the human body, is a crucial component to health and disease. Two major components to the human microbiome are the bacterial and viral communities. These communities have primarily been studied separately using metrics of community composition and diversity. These approaches have failed to capture the complex dynamics of interacting bacteria and phage communities, which frequently share genetic information and work together to maintain stable ecosystems. Removal of bacteria or phage can disrupt or even collapse those ecosystems. Relationship-based network approaches allow us to capture this interaction information. Using this network-based approach with three independent human cohorts, we were able to present an initial understanding of how phage-bacteria networks differ throughout the human body, so as to provide a baseline for future studies of how and why microbiome networks differ in disease states.