Exploring Microbiota Plasticity in the Small Intestine through Spatiotemporal Metabolic Modeling

Microbiota plasticity, the ability of microbial communities to adapt to changing environments, is crucial for understanding gut health. We develop a spatiotemporal model to simulate small intestinal microbiota and their interactions with host cells. We begin by constructing a community model of various microbial species using metabolic reconstructions and Flux Balance Analysis (FBA). By optimizing community growth, we investigate species interactions, applying L2-regularization and alternative objective formulations. The next phase incorporates enterocytes into the microbial community model. Utilizing metabolic reconstructions of S. thermophilus, F. prausnitzii, B. caccae, and E. rectale, we simulate interactions under conditions resembling an average Western diet. Our findings highlight significant interactions, including cross-feeding and competition among species. Finally, we expand the model into a spatiotemporal framework, simulating microbial dynamics along the small intestine. These simulations reveal how species abundance varies with distance and time, influenced by community composition and medium conditions.
Despite challenges in parameterization and validation, our model offers insights into the plasticity of small intestinal microbiota and their interactions with enterocytes, enhancing our understanding of gut microbiome dynamics.