Fig. 2.
Correlation network and subnetworks of the mucosal microbiome of HE patients. Connecting lines in red indicate a significant negative whereas those in blue mean a significantly positive correlation. Nodes in yellow are bacterial genera, purple are inflammatory cytokines, white are cognitive tests, blue are clinical variables, green are markers of endothelial activation, and light pink are neuroglial markers. A high score on digit symbol (DST) and targets indicates good cognition whereas a high score on the rest of the cognitive tests indicates poor performance. SDT, serial dotting; LDTt, line tracing test time; NCT-A/B, number connection test A/B. A: correlation network of the mucosal microbiome of HE patients. As can be seen, autochthonous genera belonging to the Ruminococcaceae, Lachnospiraceae, and Incertae Sedis families are associated with good cognition, lower model for end-stage liver disease (MELD) score, lower ammonia, and decreased inflammation. Subnetworks from this complex network are displayed in the following panels. B: subnetwork of the HE mucosa microbiome showing the negative correlation of the autochthonous bacteria to MELD score and inflammation. C: subnetwork of the HE mucosa microbiome showing the negative correlation of the inflammatory cytokines, particularly IL-17 with autochthonous bacteria and positive correlation with lures (indicating worse cognition with increased inflammation), endothelial activation [soluble intravascular adhesion molecule (sICAM-1)], MELD score, and nonautochthonous bacterial genera (Burkholderiaceae, Erysipelothricaceae). D: a high lure number indicates poor cognition. This subnetwork of the HE mucosa microbiome shows that lures are negatively correlated with autochthonous bacterial genera (Roseburia and Dorea) whereas they are correlated positively with Burkholderiaceae and Incertae Sedis XI and as expected with ammonia and inflammatory cytokines. E: a high number on NCT-B indicates poor performance. This subnetwork of the HE mucosal microbiome shows a negative correlation, i.e., good NCT-B performance with the abundances of Ruminococcaceae Fecalibacterium. This autochthonous genus has been associated with lower MELD score and lower inflammation (IL-17 and IL-10) and is positively correlated with other beneficial autochthonous bacteria. F: Megasphaera was significantly more abundant in HE; in this subnetwork Megasphaera abundance is significantly correlated with soluble vascular adhesion molecule (sVCAM-1) (marker of endothelial activation) and with poor cognitive performance (a high score on SDT and LDTt indicates poor whereas a high score on DST indicates good cognitive performance).