In liver cirrhosis, portal hypertension (PH) caused increased gut permeability and bacterial translocation across the gut–liver axis. Microbial DNA was found in many blood compartments recently; however, the phenomenon had not been adequately investigated in PH. For a study, the researchers sought to determine circulating bacterial DNA signatures, inflammatory cytokines, and gut permeability markers in patients with cirrhosis and PH in different blood compartments (peripheral and hepatic veins). In 58 patients with liver cirrhosis and 46 healthy controls, the 16S rRNA blood microbiome profiles were determined. The effects of taxonomic variations on PH, liver function, inflammatory cytokines, and gut permeability markers were investigated. Circulating plasma microbiome patterns in cirrhotic patients differed from the ones in controls, with Comamonas, Cruella, Dialister, Escherichia/Shigella, and Prevotella enrichment and Bradyrhizobium, Curvibacter, Diaphorobacter, Pseudarcicella, and Pseudomonas depletion. There were no differences in the abundance of taxa between the peripheral and hepatic vein blood compartments of patients with cirrhosis. In both blood compartments, Bacteroides, Escherichia/Shigella, and Prevotella enrichment were linked to severe PH (SPH); nevertheless, circulating microbiome profiles could not predict PH severity. Escherichia/Shigella and Prevotella were linked to IL-8 levels in the hepatic vein. Finally, researchers found that patients with cirrhosis had a distinct circulating blood microbiome profile, with specific bacterial genera in blood being marginally associated with SPH, Model for End-Stage Liver Disease score, and inflammation biomarkers; however, circulating microbial composition failed to predict PH severity.