Fig. 4: Specific dietary factors and metabolites show correlations with Crohn disease (CD) ileal mucosal transcriptomics signals.

WGCNA co-expression modules based on the Israel ileal (n = 41) and applied to the China transcriptomics (n = 40). Modules that were correlated with Crohn disease (CD) (p ≤ 0.05) in either Israel or China are shown. a 4 modules showed reduced and 5 were induced in CD. For each module, representative genes and enriched cells/pathways are marked. Heatmap represents the correlation between each module and different features; numbers represent the correlation p value, and color the coefficient for each comparison. b ToppFun functional annotation enrichment of genes within each module. FDR is shown as the circle size; manually selected annotations origin database is marked on the y-axis (full list in Supplementary Dataset 6). c Heatmap of the correlations between each module and dietary factors, with numbers representing the correlation p value and color for the coefficient. Only factors with p ≤ 0.05 (two-sided) in at least one module are shown, and correlations with Benjamini–Hochberg FDR ≤ 0.25 are marked with a black square. d Heatmap of the correlation between each module and stool metabolites, colored by correlation coefficient. Only metabolites with Benjamini–Hochberg FDR ≤ 0.25 in at least one module are shown, and those significant correlations (two-sided p < 0.05 and FDR ≤ 0.1, or p < 0.1 and FDR ≤ 0.25) are marked with black and gray dots respectively. e Bar graph showing the number of metabolites significantly correlated with each of the modules, separated by CD- or control-associated correlations defined by the direction of the metabolite-module correlation and the direction of the module compared to disease. The colors represent the metabolites class based on Human Metabolome Database (HMDB). f Heatmap of the correlation between each module and the 32 stool metabolites (of 91 common metabolites in the SYS and Sheba datasets) that showed significant correlation in the same direction with CD in Israel and China, colored by correlation coefficient (detailed heatmap in Supplementary Fig. 5c, full list in Supplementary Dataset 7). Metabolite’s direction is defined as the direction of the strongest correlation between all the modules. MUFA monounsaturated fatty acid, PUFA polyunsaturated fatty acid, ECM extracellular matrix.