MetaMicro · A Metabolic Theory of Microbial Ecology

Theoretical ecology has genuine potential to revolutionise microbiology, and vice versa. However, current models, such as the Lotka-Volterra equations, are typically too simplistic to apply and test rigorously. Critically, these models fail to capture microbial metabolism, which my lab and others have found central to predicting the ecology of diverse communities. My goal, therefore, is to develop a new theory of microbial ecology, rooted in metabolism, and to rigorously test it. We will capture nutrient competition, cross-feeding, interference competition and phage, and build our framework using methods from statistical mechanics. Throughout, we will experimentally test our theory using the gut microbiota as a model system. We will address three fundamental questions: 1: What determines the composition and stability of communities? Theory will be parameterised with large-scale culturing on defined media, metabolomics and whole-genome metabolic models. We will empirically test our ability to predict composition and ecological stability, and to understand the diversity-stability relationship. 2: What determines ecological success? We will study what makes a strain successful within a community, incorporating metabolism, bacterial warfare, and phage predation. 3: How does the host environment shape microbial ecology? We will employ agent-based simulations to capture spatial structure and test them with a new in-vitro organoid model of the human gut mucosa and our new in-vivo imaging pipeline for mouse microbiomes. Our plans have risk because ecological systems are complex and hard to understand. However, our work promises to deliver a step-change in both ecology and microbiology by making the study of microbial communities a predictive science, where one can understand ahead-of-time how particular sets of species will behave as a system. Furthermore, we will help establish the ecological principles needed to rationally manipulate our own microbiomes.