Fig. 4. Colonic epithelial molecular processes perturbed during IBD and in tandem with multi-omic host–microbe interactions.
a, Human DEGs (negative binomial FDR P < 0.05, minimum fold change 1.5; Supplementary Table 31) from 81 subjects with paired ileal and rectal biopsies. Ordering by diagnosis, clustering within diagnosis. IL-17 signalling (I) showed strongest enrichment in ileal DEGs (FDR P = 8.2 × 10−12)31, while the complement cascade (II)45 was enriched in rectal DEGs from patients with UC (FDR P = 5.2 × 10−8; KEGG30 gene sets, Supplementary Table 32). Example DEGs shown with I and II. b, Expression of four genes involved in host–microbe interactions26–29. Inflamed biopsy samples are shown for CD from ileum (left, n = 20, 23, 39 independent samples for non-IBD, UC, CD respectively); for CD and UC in rectum (right column; n = 22, 25, 41 independent samples for non-IBD, UC, CD); non-IBD samples were non-inflamed. Asterisks indicate significant differential expression compared to non-IBD (Fisher’s exact test, FDR P < 0.05; P values in Supplementary Table 31). Boxplots show median and lower/upper quartiles; whiskers show inner fences. c, Significant associations among 10 aspects of host–microbiome interactions: metagenomic species, species-level transcription ratios, functional profiles captured as EC gene families (MGX, MTX and MPX), metabolites, host transcription (rectum and ileum), serology, and calprotectin (sample counts in Fig. 1b, c). Network shows top 300 significant correlations (FDR P < 0.05) between each pair of measurement types (for serology, FDR P < 0.25). Nodes coloured by disease group in which they are ‘high’, edges by sign and strength of association. Spearman correlations use residuals of a mixed-effects model with subjects as random effects (or a simple linear model when only baseline samples were used (biopsies)) after covariate adjustment (see Methods). Time points approximately matched with maximum separation 4 weeks (see Methods). Singletons pruned for visualization (Extended Data Fig. 8). Hubs (nodes with at least 20 connections) emphasized.