Ascites bactericidal capacity in patients with decompensated cirrhosis

BACKGROUND & AIMS: Patients with decompensated cirrhosis are at high risk of developing bacterial infections. The most common infection is spontaneous bacterial peritonitis (SBP) in ascites fluid (AF), caused by gut bacterial translocation and facilitated by cirrhosis associated immune dysfunction. Common causative agents of SBP are thought to represent pathobionts that increase in abundance in the gut with cirrhosis severity, rather than opportunistic commensals. Despite this there have been few studies describing the characteristics of SBP pathogens and immune responses to them. METHODS: We investigated the bactericidal capacity of cell-free AF and ascites macrophages. RESULTS: cells, phagocytosed and killed ExPEC and non-pathogenic E. coli K-12 with similar efficacy. Mice with toxin-induced cirrhosis had higher bacterial burdens in the liver compared to control mice when infected with ExPEC¸ but rapidly cleared an rfaH mutant attenuated for capsule and O-antigen biosynthesis. CONCLUSION: These data highlight the importance of understanding bacterial virulence profiles in addition to taxonomy in cirrhosis dysbiosis and identify critical roles for capsule and O-antigen in host evasion by SBP-associated pathogens. Targeting bacterial virulence factors and/or host macrophage functions may reduce the risk of SBP in cirrhosis.