Fig. 3

Integrated association of the differential gut microbial features with fecal metabolites, CCHD versus HC. A, B Overview of the significant associations between multilevel microbial features and fecal metabolites. The significant associations between continuous microbial variables (microbial abundance, metabolic pathways, and vSVs) and fecal metabolites are determined by Spearman’s rank correlation analysis and shown in Circos plot A; whereas the significant associations between binary microbial variables (dSVs) and fecal metabolites are determined by Mann–Whitney U test and shown in heatmap B. The associated microbial features and metabolites are identified in the comparison of CCHD and HC. Other metabolites include lipids, amino acids, nucleotides, and carbohydrates. C Heatmap of multiple associations between microbial abundance (Bifidobacterium, Enterobacter, and Enterococcus) and fecal metabolites (Spearman’s rank correlation analysis). Only significant associations are plotted. D Scatter plots showing positive associations between Enterococcus faecium and 3-nitrotyrosine and Bifidobacterium longum and l-fucose. E Scatter plot showing positive association between a 2-kbp vSV in the Escherichia coli genome and leukotriene F4. F Heatmap of multiple associations between vSVs in Bifidobacterium bifidum PRL2010 and fecal metabolites (Spearman’s rank correlation analysis). Only significant associations are plotted. G Boxplots (center, median; box, IQR; whiskers, IQR × 1.5; dots, outliers) showing the relative abundance of 2-fucosyllactose in individuals harboring an 8-kbp dSV in the Enterococcus faecalis ATCC29212 genome (blue, n = 18) and individuals with no deletion (red, n = 18), and the relative abundance of hydroxyphenyllactic acid in individuals harboring a 21-kbp dSV in the Bifidobacterium longum genome (blue, n = 8) and individuals with no deletion (red, n = 40). Significance is determined by Mann–Whitney U test. CCHD, critical congenital heart disease; HC, healthy control; AA, arachidonic acid; HMOs, human milk oligosaccharides; AAA, aromatic amino acid; PUFAs, polyunsaturated fatty acids; SCFAs, short chain fatty acids; IQR, interquartile range; dSV, deletion structural variation; vSV, variable structural variation