Resource Competition and Host Feedbacks Underlie Regime Shifts in Gut Microbiota

AbstractThe spread of an enteric pathogen in the human gut depends on many interacting factors, including pathogen exposure, diet, host gut environment, and host microbiota, but how these factors jointly influence infection outcomes remains poorly characterized. Here we develop a model of host-mediated resource competition between mutualistic and pathogenic taxa in the gut that aims to explain why similar hosts, exposed to the same pathogen, can have such different infection outcomes. Our model successfully reproduces several empirically observed phenomena related to transitions between healthy and infected states, including (1) the nonlinear relationship between pathogen inoculum size and infection persistence, (2) the elevated risk of chronic infection during or after treatment with broad-spectrum antibiotics, (3) the resolution of gut dysbiosis with fecal microbiota transplants, and (4) the potential protection from infection conferred by probiotics. We then use the model to explore how host-mediated interventions-namely, shifts in the supply rates of electron donors (e.g., dietary fiber) and respiratory electron acceptors (e.g., oxygen)-can potentially be used to direct gut community assembly. Our study demonstrates how resource competition and ecological feedbacks between the host and the gut microbiota can be critical determinants of human health outcomes. We identify several testable model predictions ready for experimental validation.