Metabolic bottlenecks and shadow price profiles computed when optimizing for Iso-CA production in 194 microbiome community models. a Abundance of the 3β-HSDH reaction yielding Iso-CA (VMH ID: ICA3bHSDHe) plotted against Iso-CA production potential (flux values are given in mmol gDW−1 h−1) for the 194 microbiomes. b Heat map of the shadow prices retrieved from the 194 microbiomes when the production of two deconjugated primary and 13 secondary bile acids was optimized. Blue and white data points show nonzero and zero shadow prices, respectively. The columns show the 194 microbiomes annotated by group. The rows show all metabolites that had a nonzero shadow price in at least one community model. The metabolites are annotated by taxonomy. Entries annotated with “Diet_metabolite” represent bile acid metabolites present in the dietary, luminal, or fecal compartment of the microbiome model. The “bile acid optimized” color bar shows the bile acid for which production was optimized. c Number of metabolites with nonzero shadow prices in the microbiome models of healthy adults, IBD patients, and healthy pediatric controls. Significant difference (p value < 0.001) is indicated by stars. d Shadow prices for the biomass metabolite of Holdemania filiformis DSM 12042, a strain carrying 3α-HSDH but not 3β-HSDH, plotted against Iso-CA production and abundance of the 3β-HSDH reaction. Blue dots indicate models belonging to Scenario 2 (see main text). e Shadow prices for the biomass metabolite of Collinsella aerofaciens ATCC 25986, a strain carrying 3β-HSDH but not 3α-HSDH, plotted against Iso-CA production and abundance of the 3β-HSDH reaction. Blue dots indicate models belonging to Scenario 3 (see main text). f Shadow prices for the biomass metabolite of Ruminococcus gnavus ATCC 29149, a strain carrying both 3α-HSDH and 3β-HSDH, plotted against Iso-CA production and abundance of the 3β-HSDH reaction. g Pathway for Iso-CA biosynthesis from Glyco-or Tauro-CA, and depiction of the steps representing bottlenecks in Scenarios 2 and 3 (see main text). For metabolite abbreviations see Table 1. For simplicity, sections of the y axis without any data are omitted in a and d–f (indicated by the two gray lines).