Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis

Abstract

BACKGROUND Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease, and gut microbiota dysbiosis is associated with both of them. AIM To assess the relationship between gut dysbiosis and cardiovascular risk (CVR) in an experimental model of steatohepatitis. METHODS Adult male Sprague-Dawley rats were randomized to a control group (n = 10) fed a standard diet and an intervention group (n = 10) fed a high-fat choline-deficient diet for 16 wk. Biochemical, molecular, hepatic, and cardiac histopathology. Gut microbiota variables were evaluated. RESULTS The intervention group had a significantly higher atherogenic coefficient, Castelli’s risk index (CRI)-I and CRI-II, interleukin-1β, tissue inhibitor of metalloproteinase- 1 (all P < 0.001), monocyte chemoattractant protein-1 (P = 0.005), and plasminogen activator inhibitor-1 (P = 0.037) than the control group. Gene expression of miR-33a increased (P = 0.001) and miR-126 (P < 0.001) decreased in the intervention group. Steatohepatitis with fibrosis was seen in the intervention group, and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance (P = 0.007), reduction in the mean area of cardiomyocytes (P = 0.037), and an increase of atrophic cardiomyocytes (P = 0.007). There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and CVR. The intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota (both P < 0.001) than controls. Nine microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and CVR. CONCLUSION The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.