Metabolic modulation in liver by glucan from Enterococcus hirae (OL616073) via gut-liver axis culture model of steatosis

Metabolic dysfunction associated fatty liver disease (MAFLD) starts with increased fat deposition called steatosis progressing towards steatohepatitis, fibrosis, cirrhosis and end stage liver disease. Dysfunctional metabolism in type-2 diabetes or obesity is associated with gut dysbiosis, causing release of gut microbial endotoxins like lipopolysaccharides (LPS) into the liver via portal circulation also known as gut-liver axis. Endotoxins or LPS signals metabolic changes in the liver initiating steatosis via gut-liver axis. Various pre-clinical models have been studied to evaluate the role of fermented food derived bioactive compounds, thus, preventing the process of steatosis. Among them exopolysaccharides (EPS), as a part of fermented foods have been reported to produce metabolites as a result of gut microbial fermentation, providing liver with health benefits in the form of hypolipidemic, anti-inflammatory and anti-oxidant effects. In the present study, we have evaluated the role of a noble EPS or G (glucan) in the condition of liver steatosis using cell culture model of gut-liver axis by co-culturing Caco-2 and HepG2 cells in transwell culture dishes. LPS was used as an agonist to mimic gut dysbiosis in caco-2 cells in the upper chamber, with or without pre-treatment of G. HepG2 cells cultured in lower chamber were extracted for intracellular metabolites to be analyzed by LC-Q-TOF. The global metabolomic profiles of LPS+G+ and LPS+ treated cells were compared. The primary target of G showed its role in cholesterol and primary bile acid metabolism along with changes in nucleotide, vitamins and branched chain aminoacid metabolites helpful in reducing fatty liver. Future studies with this glucan using targeted metabolomics could confirm biomarkers of therapeutic intervention of steatosis and could be translated into healthy food products with health benefits especially to the liver.