Obeticholic Acid Decreases Intestinal Content of Enterococcus in Rats With Cirrhosis and Ascites

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. (Hepatology Communications 2021;0:1-11).

Comprehensive bibliometric and visualized analysis of research on gut-liver axis published from 1998 to 2022

“…BA signals mediate the homeostasis of BA, lipids, and glucose through nuclear (hormone) receptors, such as FXR and GPCRs, and the control of innate/adaptive immunity. BA signals also perform the crucial functions of regulating liver metabolism, shaping gut microbiota, maintaining intestinal integrity, and preventing bacterial translocation [ [62] , [63] , [64] , [65] ]. Therefore, BA and its derivatives can be used as potential liver disease therapies.…”

Therapeutic possibilities of gut microbiota modulation in acute decompensation of liver cirrhosis

“…For example, oral administration of obeticholic acid to rats with a model of CCl4-induced LC reduced the intestinal content of the genus Enterococcus spp . [ 70 ] and decreased the bacterial translocation[ 71 ]. Besides, obeticholic acid prevented the increased expression of monocyte chemoattractant protein-1 following stimulation with TNF-α and lipopolysaccharides or TNF-α alone in liver sinusoidal endothelial cells and Kupffer cells in rats with a model of thioacetamide-induced LC[ 72 ].…”