Enteroscape: An agent-based model for simulating microbial dynamics and host responses in the gut ecosystem

Understanding microbial interactions within the gut microbiome is challenging due to the sheer number of microorganisms present. Each additional microbe introduces new layers of complexity, especially when studying the conditions and dynamics of infectious progression. To address this challenge, we have developed Enteroscape: an in silico agent-based model, grounded in previous research, laboratory experiments, and in vivo assays. Enteroscape enables simulation of diverse microbial interactions within a nematode host environment. In this study, we used Enteroscape to model the progression of pathogenic yeast infection and evaluate the effects of probiotic yeast treatment in the Caenorhabditis elegans intestine. Drawing upon empirical and literature-based behavioral rules for individual microbes, Enteroscape simulations produced emergent behaviors of the microbial population that mirror experimentally observed infection dynamics, including visual patterns of infectious progression, as well as the effect of probiotic treatment on the host lifespan. Enteroscape demonstrates how computational models can generate testable predictions that deepen our insight into microbial community interactions and their impact on host biology. Author SummaryThe human microbiome is a complicated ecosystem, consisting of trillions of microbes of hundreds of different species that live in the human intestine. Understanding how different species interact to maintain a healthy balanced microbiological ecosystem that keeps pathogenic microbes at bay is critically important to human health. We have developed a simple experimental system that allows us to examine the interactions of just a few thousand microbes at a time in a living host, the microscopic nematode worm, C. elegans. In prior laboratory work, we have demonstrated how ingestion by the worm of the human pathogenic microbe C. albicans shortens the worms lifespan, while co-ingestion of various probiotic microbial species restores a longer lifespan. In this paper, we report the creation of a computational model of this system, which we named Enteroscape. We show that Enteroscape mimics the results of the experimental system, including the visual progression of infection by a pathogenic species, the effects on worm lifespan, and the amelioration of the pathogens effects by a probiotic species. Enteroscape will allow us to develop and test hypotheses about the mechanisms underlying remediation by probiotic microbes, with potential applications to better probiotic treatment of human infections.