The human gut microbiome provides a number of critical functions for human health, including the digestion of otherwise indigestible substrates and protection against pathogen expansion. Healthy gut conditions are maintained in part through positive feedback loops which involve both the host and anaerobic mutualists adapted to persist in the anoxic gut environment. However, opportunistic pathogens can exploit similar positive feedback systems in the gut to enable exponential expansion and chronic infection. While the interacting/opposing feedbacks of many enteric pathogen systems have been studied and described in detail, there has been little work drawing them together to identify commonalities, and to explore ways in which ecological principles could be leveraged to develop alternative treatments alongside more traditional targeted mechanism-specific treatments. Here, we introduce a general ecological framework and mathematically explicit model aimed to understand, predict, and deter pathogen expansion in the gut.
Results/Conclusions
Our model provides several specific insights into gut community dynamics and their relationship to pathogen expansion. First, the greater the population of mutualistic obligate anaerobes, relative to the population of the pathogen, the less likely it is for pathogen exposure or a general disturbance to lead to chronic gut dysbiosis. Second, by reducing the overall cell count, antibiotic treatments (e.g., to treat pathogen infection) paradoxically increase the risk of falling into another basin of attraction and resulting in chronic infection. Third, the host may subvert the deterministic nature of gut community dynamics by altering the input rates of key resources, particularly oxygen, leading to qualitatively different community outcomes. To conclude, we customize and use our model to better understand the results of a murine experiment on post-antibiotic spread of Enterobacteriaceae in the gut.