Fig. 6

Mediation linkages among the gut microbiome, metabolites, and serum biomarkers of intestinal permeability and inflammation. A Sankey diagram illustrating the 23 significant mediation linkages among gut microbiome, fecal metabolites, and serum biomarkers of intestinal permeability and inflammation. Columns from left to right show microbial features (including microbial abundance and metabolic pathways), fecal metabolites, and serum biomarkers, respectively. The curved lines across the columns indicate the mediation effects and the colors correspond to different biomarkers. B–G Examples of mediation linkages among gut microbiome, metabolites, intestinal barrier dysfunction, and systemic inflammation inferred by bi-directional mediation analysis. The beta coefficient and significance are labeled at each edge, and the proportions of mediation effects are labeled at the center of the ternary diagrams. The red arrows indicate the gut microbial effects on serum biomarkers mediated by metabolites, whereas the blue arrows indicate the reverse mediation effects, that is, the microbial effects on metabolites mediated by serum biomarkers. P_medi and P_inv.medi are estimated by using the bi-directional mediation analysis. Asterisks indicate statistical significance for all panels: *P < 0.05, **P < 0.01, ***P < 0.001. 13-HODE, 13S-hydroxyoctadecadienoic acid; 9(S)-HODE, α-dimorpholic acid; IL, interleukin; IFN-γ, interferon-γ; TNF-α, tumor necrosis factor-α; LPS, lipopolysaccharide; iFABP, intestinal fatty acid binding protein; LBP, lipopolysaccharide binding protein