Fig. 4: Microbiome and metabolome features linked with IHD and its dysmetabolic pre-morbidities.

Using the categorization scheme described in Fig. 3 and Extended Data Fig. 4, gut microbiome and metabolome markers were categorized as DMFs, IHDFs, ESCFs or DSCFs, of which IHDFs (a), ESCFs (b) and DSCFs (c) are displayed here. In each panel, arrow length shows effect sizes (Cliff’s delta) for respective group comparisons. Cliff’s delta for HC versus IHD comparisons are displayed for IHDFs (a), whereas Cliff’s delta for both HC versus MMC and MMC versus IHD are displayed for ESCFs (b) and DSCFs (c), with arrowhead pointing to the direction of change. Only features exhibiting an absolute effect size greater than 0.1 are displayed, inclusive of serum metabolites, metagenomic species and microbial density indices (see Supplementary Table 17 for a description of effect sizes and confounding status). Two-sided MWU was used for assessing the significance of group-wise comparisons using HC (n = 275), MMC (n = 372), UMMC (n = 222) and IHD (n = 372) groups. Multiple testing corrections were done using the Benjamini–Hochberg method, and FDR ≤ 0.1 was considered significant. *The metabolite was not validated by an internal standard but confirmed with great confidence according to information from Metabolon (Methods) who performed the analysis. **An internal standard for the metabolite was not available but was confirmed with reasonable confidence according to information from Metabolon (Methods) who performed the analysis.