Fig. 5

Triangular relationship among diabetes-associated microbial genera, metabolites, proteins, and prevalent diabetes (N = 426). A Mediated association of gut bacterial genera with prevalent diabetes by selected metabolites (or lipid modules) and proteins. The left forest plot shows associations of selected genera with diabetes following consecutive adjustment for selected metabolites/proteins in logistic regression. The “base model” refers to the model adjusted for age at visit, study site, race/ethnicity, household annual income, education, smoking, alcohol consumption, HIV serostatus, fasting status, and antibiotics use. “+ metabolites/proteins” refer to the models further adjusted for specific metabolites/proteins in addition to variables in the base model, while “+ All” refer to the model further simultaneously adjusted for all selected metabolites/proteins. The right panel shows proportions mediated (calculated as the ratio of indirect effects to total effects) of examined metabolites (or lipid modules) and proteins in regression-based mediation analysis (see “ Methods”). B An alluvium plot summarizing significant mediation effects of individual proteins and metabolites in the association between bacteria and diabetes (P < 0.05). “Blue” alluvia belts refer to the potential pathway indicating the negative associations of bacteria with diabetes, while “red” ones refer to pathways exhibiting positive associations of bacteria with diabetes. Size of alluvium flow refers to the relative magnitude of mediated proportions. C A network showing the interrelationship (presented as partial correlation coefficients) among omics signatures (genera: marked as blue; metabolites: red; proteins: green) in associations with prevalent diabetes. The colors of lines refer to the direction of correlation (positive: orange; negative: blue). For interrelationship among signatures within each omics class, only |partial coefficient|> >0.25 with FDR-q < 0.1 were presented. GDNF: glial cell line-derived neurotrophic factor, HGF: hepatocyte growth factor, IL-18R1: interleukin-18 receptor 1, IL6: interleukin-6, LIF-R: leukemia inhibitory factor receptor, OPG: osteoprotegerin, OSM: oncostatin-M, CD6: T cell surface glycoprotein CD6 isoform, CSF-1: macrophage colony-stimulating factor 1, FGF-21: fibroblast growth factor 21, DMGV: dimethylguanidino valerate