Fig. 3: Functional relevance of structural variations (SVs) in human gut microbiome.

a The top 30 categories in functional enrichment of SV-affected genes based on KEGG, metabolism-related pathways account for 19; p-values were from Fisher’s test. b SVs influencing the gut bacteria-fecal metabolite correlations, upper panel indicates significant correlations (Spearman correlation, FDR < 0.1), the presence of SVs abolished significant correlations (lower panel, all p-values > 0.05) and the subgroup without SVs maintained significance (middle panel, all p-values < 0.05). Colors denote different bacterial species. c Overview of SV-affected bacteria-metabolite correlation pairs (Spearman). Colors and bars denote different bacteria and metabolites. d Fusicatenibacter saccharivorans was significantly correlated with neotrahlose (NSV, n = 100), SVs within gene K03655 lead to insignificant correlations (SV1, n = 52; ρ (rho) = 0.032, p = 0.82), and different from the other subgroup/strain (SV0, n = 48; ρ = 0.45, p = 0.0015, FDR = 0.099). e Similar case for correlation between A. rectalis and Fructose-1-phosphate (F1P), SVs at K01193 leads to strain-level differences. f, g Fecal neotrahlose and F1P concentrations were significantly correlated with blood glucose (n = 100). h For F. saccharivorans, SVs within K03655 gene cause insignificant associations with blood glucose (SV1, n = 52; ρ = −0.20, p = 0.15), and the subgroup without SVs was significantly correlated with blood glucose (SV0, n = 48; ρ = −0.54, p = 8.6e-5, FDR = 0.001). i Similarily, for A. rectalis, SV within gene K01193 also leads to strain-level differences in correlation with blood glucose (SV0, p = 0.05, n = 46; SV1 group n = 54). The ρ (rho) indicates the coefficient of spearman correlation, and p-values were adjusted with Benjamini-Hochberg procedures for FDR control. The shadings in (d–i) indicate the 95% confifence intervals (CI) and colors in d–i indicate different groups. NSV: all sample; SV0: subgroup without SV in bacterial gene; SV1: subgroup with presence of SV in bacterial gene. The details of subgroups are available in the Supplementary Data 6.