Abstract
The intestinal microbiome and bacterial translocation (BT), the passage of microorganisms from the gut lumen to mesenteric lymph nodes and other extra-intestinal sites, are main mechanisms implicated in liver injury and further decompensation in patients with cirrhosis. We hypothesized that obeticholic acid (OCA), a semisynthetic bile acid, would change the microbiome composition and reduce bacterial translocation in experimental cirrhosis. Rats with cirrhosis induced by carbon tetrachloride inhalation (a nonseptic model) with ascites present for at least 7 days were randomized to receive a 14-day course of OCA at a dose of 5 mg/kg/day (n = 34) or placebo (n = 34). Stool was collected at days 1 (randomization), 8, and 14 (sacrifice) for analysis of intestinal microbiome using the V4 hypervariable region of the bacterial 16S gene amplified by polymerase chain reaction. Bacteriological cultures of mesenteric lymph nodes, blood, and ascites were performed at end of study. Twenty-four animals in each group reached the end of study. Compared with placebo, rats treated with OCA had decreased relative abundance of Enterococcus in both ileum content (P = 0.02) and in stool (P < 0.001). BT from pathogenic bacteria was not different between groups. At end of treatment, rats on OCA had a significantly lower aspartate aminotransferase (AST) (266 vs. 369 IU/L; P < 0.01) and higher serum albumin (0.9 vs. 0.7 g/dL; P < 0.01) than rats on placebo. Conclusion: Although OCA did not appear to reduce BT by pathogenic bacteria, the reduction in intestinal content of Enterococcus, which has been associated with hepatocyte death, in OCA-treated animals is consistent with our observed improvements in AST and in liver function, as evidenced by higher serum albumin.