Using metagenomics and discovering over 3 million genes, constituting a ‘parts list’ of this ecosystem, key species were identified. Here we reconstructed genome-scale models (GEMs) for three key species, iBth801 (Bacteroides thetaiotamicron), iEre400 (Eubacterium rectale), iMsi385 (Methanobrevibacter smithii), iBif452 (Bifidobacterium adolescentis L2-32) and iFap484 ( Faecalibacterium prausnitzii A2-165) as relevant representatives of the three main phyla in the human gut (Bacteroidetes, Firmicutes and Euryarchaeota). These GEMs allow for improved annotation of metagenomics data, but will more importantly enable simulation of the gut microbiome ecosystem. Hereby it will be possible to gain information about the functional role of different species in this complex ecosystem as well as evaluate the role of different species in silico. Our modeling will hereby become an important bridge between clinical data and rodent experiments, as the modeling will allow for experimental design.