Fig. 3: Model-predicted host–microbiome interactions.

a, Structure of the metamodel. The solid borders indicate compartments of the metamodel. The black arrows indicate metabolite exchanges between compartments. The dashed borders indicate compartments represented only by exchange reactions. The white arrows indicate the direction of metabolic exchanges along the bloodstream. BBB, blood–brain barrier. b, Frequency of microbiome dependence of metabolite import (positive) and export (negative) across organs. Metabolites with the highest frequency of exchange across 52 models are shown (Supplementary Table 3.2). For metabolite abbreviations, see Supplementary Table 3.2. c, Microbiome dependency of microbiome-responsive host genes in a cohort of GF, conventionalized and conventionally raised mice (n = 8 each). The y axis indicates sets of genes differentially regulated in tissues and contrasts; the x-axis shows the microbiome dependency of corresponding reactions. ‘Shared’ indicates genes regulated in at least three tissues. FDR-corrected P values of Dunn’s tests following a group-level Kruskal–Wallis test are shown next to the bar plots of means with error bars representing the standard deviation. Only comparisons with a Kruskal–Wallis test P < 0.05 are shown. *P < 0.05; **P < 0.01; ***P < 0.001. Exact P values are provided in Supplementary Table 3.11. d–f Subsystem enrichment of model-predicted interactions between host and microbiome reactions for subsystems connected with at least two host subsystems and an FDR-corrected enrichment P < 10⁻⁴ (one-sided Fisher’s exact test; Supplementary Tables 3.3–3.5). For pathway abbreviations, please see Supplementary Tables 3.3–3.5.