Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2052
Peer-review started: April 1, 2021
First decision: July 16, 2021
Revised: July 20, 2021
Accepted: October 18, 2021
Article in press: October 18, 2021
Published online: December 27, 2021
Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease, and gut microbiota dysbiosis is associated with both of them.
To assess the relationship between gut dysbiosis and cardiovascular risk (CVR) in an experimental model of steatohepatitis.
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.
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.
The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.
Core Tip: Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease (MAFLD) and gut microbiota dysbiosis is associated with both. Among the risk factors, we report significant correlations between the presence of atherogenic dyslipidemia, systemic inflammation, endothelial dysfunction, liver fibrogenesis, and gut dysbiosis, all of which contributed to the progression of MAFLD and increased cardiovascular risk.