Figure 2

Faecal metabolomics and network analysis. The Mann-Whitney U test was employed to assess putative differences among faecal metabolites (from NMR) of cirrhotic patients (red) and controls (green) (panel A). Scaled values on the y-axis are arbitrary units referring to peak area. P values: *≤0.05, **≤0.01. PICRUSt analysis (panel B) was employed to predict metagenomes from the 16S data and to infer differences in mean proportions (expressed as %) among cirrhotic patients (red) and controls (green), for the first 20 Kegg Orthologues (KOrths) ordered by decreasing effect size (η²). The specific mean contributions of bacterial phyla and genera to the 10 KOrths overrepresented and to the 8 KOrths underrepresented in cirrhotic patients were calculated with PICRUSt (see supplementary Fig. S4). Co-occurrence network analysis was performed on faecal 16S and NMR merged datasets for both controls (panel C) and cirrhotic patients (panel D). The Pearson coefficient (r), ranging from positive (blue) to negative (red) values, is reported (edges with −0.7 > r > 0.7), based on correlation heatmaps (see supplementary Fig. S5). The edge thickness is proportional to the number of co-occurrences found between two nodes (species or metabolites) linked by the edge itself. Bacterial species having a mean relative abundance ≥0.5% were reported with their OTU number (squared brackets) and represented as circles, while metabolites were represented as squares within networks. Node size is proportional to the number of edges departing from the node, indicating its degree of interaction. Node name size is proportional to the betweenness centrality, meaning the bridging/key importance of that node within the network. Nodes are coloured by modularity class (community detection algorithm) to identify different functional metagenomic communities (FMCs) for the controls (5 FMCs) and cirrhotic patients (2 FMCs).