Fig. 5: Multi-omic network analysis, metabolomics in mice supplemented with Lactobacilli and validation of glutathione in vitro.

a Multi-omic network integrating gene expression of genes significantly regulated in liver by Lactobacilli (circles), liver lipid profile (diamonds), and systemic metabolic parameters (squares) with red symbols indicating upregulated and blue are down in Lactobacilli supplemented mice. Green outline of nodes indicates significantly decreased lipid or phenotype; size of circle corresponds to the combined score of degree and bipartite betweenness centrality (BiBC) in the network. The orange and black edges indicate positive and negative correlations, respectively. Genes with top degree and BiBC are indicated. Source data are available at https://tinyurl.com/multi-omic-NW-Fig-5A. b Gene ontology biological functions over-represented in the genes of multi-omic network. c Scatterplot showing the degree and BiBC of all nodes in the multi-omic network with genes (gray), lipids (blue), phenotypes (green). d Fold-changes of 133 serum metabolites in germ-free (GF) mice fed western diet (WD) and colonized with L. gasseri for 2 weeks in comparison with GF mice on WD (n = 2 per group). TG, Triacylglycerol (16:0/18:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)); MG, Monoacylglycerol; 8-iso-15-keto PGF2α, 8-iso-15-keto Prostaglandin F2α. Source data are provided in Supplementary Supplementary Data S14. e Changes in 12 metabolites identified in Fig. 5d in specific-pathogen mice (SPF) fed WD (data of serum pools of 4–6 mice in each pool per group), in five experiments of Lactobacilli-supplemented mice, mean fold change across five experiments and FDR (false discovery rate) is plotted. Source data are provided in Supplementary Supplementary Data S14c. f Left heatmap shows the geometric mean of normalized gene expression in AML-12 cells treated with either low sugar medium (glucose 17 mM), high sugar medium (glucose and fructose at 50 mM each) or high sugar medium supplemented with 4 mM, 6 mM, or 9 mM of reduced glutathione (GSH) ethyl ester (5–6 independent experiments). The right heatmap shows geometric mean of normalized gene expression from RNA-Seq in liver of western diet (WD) fed mice or WD-fed mice supplemented with either L. gasseri or L. johnsonii (red, high; blue, low relative gene expression). Source data are provided as a Source Data file.