Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection

Abstract

Background and Aims: Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock. However, variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in de-compensated cirrhosis (DC) patients with infection remain unknown. Methods: We conducted 16-srRNA sequencing on stool samples (n=51: sepsis, 27/no sepsis, 24) collected from consecutive DC patients upon admission. Bacterial di-versity, significant taxa, and respective metabolic profiling were performed based on subgroup comparisons. Conet/ Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events. Results: Genera associated with patho-genicity in conditions of immune exhaustion (Corynebacte-rium, Lautropia) were predominant in patients with sepsis. Metabolic pathways associated with oxidative stress and endotoxemia [lipopolysaccharide (LPS) synthesis and sulfur relay] were significantly upregulated in sepsis. Specific taxa were associated with sites of infection in DC patients. Protective oxidant pathways that increase glutathione were upregulated in those without sepsis. Gammaproteobacte-ria family of sulfur-metabolizing bacteria, exaggeration of orally predominant pathogens (Prevotella), and pathways of severe LPS-related hyperinflammatory stress were nota-ble in those with interleukin-6 levels >1,000 pg/dL. Path-ogenic genera related to an immune deficient state was significant in DC with ≥2 infection episodes. Megamonas was associated with survival during the same admission. Conclusions: Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC. Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis, for which larger prospective, well controlled population-based stud-ies remain an unmet need.