Figure 3

Metabolic pathways with an altered flow in enteroids generated from patients with Crohn's disease (CD) versus control patients: Our Flux Balance Analysis/Random Forest framework was applied to RNA sequencing data from enteroid models generated from n = 16 patients with Crohn's disease and n = 12 healthy controls. After obtaining the list of top metabolic reactions that were altered between the CD and control groups, these reactions were grouped into "families" (A–D) based on the biological processes they were involved in. (A) ROS detoxification: superoxide dismutase and catalase, (B) Glycerophospholipid metabolism: choline phosphatase and the transport of phosphatidylserine. (C) Fatty acid oxidation: RE3121R is involved in pentaenoyl coenzyme A metabolism and palmitoyl coenzyme A hydrolase (D) Sphinganine transport. For all graphs, the x-axis describes the reaction that is altered between controls (orange) and diseased states (blue). The y-axis shows the flux values generated by RIPTiDe by analyzing the flow of metabolites through an ileal-specific metabolic network reconstruction. The scale of flux values (y-axis) varies with the reactions as the efficiency of different metabolic pathways in generating biomass varies in a given biological system. A Mann–Whitney U test was done to compare reactions that were varied between patients with Crohn's disease and controls. The stars (*) are used to flag levels of significance. *p < 0.05, **p < 0.01, ***p < 0.001, ns: not significant. ROS: reactive oxygen species.