[51] Further, they have increased intestinal permeability and bacterial translocation, caused in part by portal hypertension and vascular congestion. Culture-independent techniques targeting the hypervariable 3 region of the bacterial 16S rRNA gene have shown a reduced microbial diversity and reduction

in Bacteroidetes, and an increase in Proteobacteria and Fusobacteria in patients with liver cirrhosis.[52] Although the exact reason for these changes remains unclear, reduced intestinal motility, decreased gastric acidity and pancreato-biliary secretions, and portal hypertensive enteropathy may all contribute. In an experimental EPZ015666 molecular weight mouse model of liver fibrosis, expression of profibrogenic genes (including transforming growth factor-β, matrix metalloproteinase-2, procollagen α-1, and tissue inhibitor of metalloproteinase-1), serum levels of pro-inflammatory cytokines (TNF-α and IL-6) and bacterial translocation showed progressive increase with increasing fibrosis.[53] Thus, the available data suggest a possible role for altered gut microbiota in liver fibrogenesis. However, majority of data that suggest

a pathogenetic relationship are based on animal studies. Human data on the association are limited to observational studies showing qualitative and quantitative alterations in gut microbiota in cirrhosis and are currently Montelukast Sodium SCH727965 research buy inadequate to prove a cause–effect relationship. The clinical course of liver cirrhosis is frequently complicated by development of GI bleed, HE, renal failure, or spontaneous bacterial peritonitis (SBP), leading to a detrimental effect on liver function and poorer clinical outcomes. Altered gut microbiome may also influence the risk of development and outcome of these complications. Patients with cirrhosis have an increased

risk of hospital-acquired infection than non-cirrhotic controls. Common bacterial infections in patients with liver cirrhosis include SBP, respiratory tract infections, urinary tract infection, and generalized sepsis. A large majority of these infections are caused by gram-negative enteric bacilli, suggesting an origin in the gut. Patients with chronic liver disease have an overgrowth and translocation of gut bacteria, as evidenced by an increased presence of bacterial DNA[54] as well as antibodies against microbes[55] in their circulation. Intestinal permeability is increased in cirrhotics with ascites, history of SBP, and higher Child–Pugh score.[56] In one study, the bacteria showing translocation from bowel to mesenteric lymph nodes belonged mostly to Enterobacteriaceae family, Enterococcus group and some Streptococcus species,[57] that is similar to those causing infections in patients with cirrhosis.