Genome-scale metabolic modeling of the human gut bacterium Bacteroides fragilis strain 638R

by Maxwell Neal, Deepan Thiruppathy, Karsten Zengler

Bacteroides fragilis is a universal member of the dominant commensal gut phylum Bacteroidetes. Its fermentation products and abundance have been linked to obesity, inflammatory bowel disease, and other disorders through its effects on host metabolic regulation and the immune system. As of yet, there has been no curated systems-level characterization of B. fragilis’ metabolism that provides a comprehensive analysis of the link between human diet and B. fragilis’ metabolic products. To address this, we developed a genome-scale metabolic model of B. fragilis strain 638R. The model iMN674 contains 1,634 reactions, 1,362 metabolites, three compartments, and reflects the strain’s ability to utilize 142 metabolites. Predictions made with this model include its growth rate and efficiency on these substrates, the amounts of each fermentation product it produces under different conditions, and gene essentiality for each biomass component. The model highlights and resolves gaps in knowledge of B. fragilis’ carbohydrate metabolism and its corresponding transport proteins. This high quality model provides the basis for rational prediction of B. fragilis’ metabolic interactions with its environment and its host.