A computational tool for investigating mechanistic relationships in the colon-diet-flora complex
The composition of the microflora inhabiting the colon and its affect on health has been a topic of international and cross-disciplinary interest for the better part of this century. With the advance of laboratory experiment and data acquisition techniques, there exists an excess of observation-based hypotheses circulating the gut literature. Many of these hypotheses have limited mechanistic evidence due to significant variability in methods and results. The general costs of experimentation make systematic and repeated investigation for improved reliability challenging. The compuGUT is a simulation tool developed to aid in the construction of mechanistic understanding underlying the interactions of intestinal microflora and their physical environment. It can be used to test existing hypotheses, evaluate contradictory claims, and suggest novel mechanisms. In this thesis I describe: (1) The construction of the underlying deterministic models, (2) the development and analysis of the compuGUT as a software tool, and (3) preliminary simulation investigations with potential biological implications, through the presentation of published and unpublished manuscripts and communications. The compuGUT is an important development in promoting a modeling-experimental iterative approach to studying intestinal microbiota. It will guide detailed investigation of the microbiota, its interactions, and its affects on health.