Metabolomics reveals the effects of Lactiplantibacillus plantarum dy-1 fermentation on the lipid-lowering capacity of barley 13-glucans in an in vitro model of gut-liver axis

Bioactive polysaccharides known as the biological response modifiers, can directly interact with intestinal epithelium cells (IEC) and regulate key metabolic processes such as lipid metabolism. Here, the coculture of Caco-2/HT29 monolayer (>400 Cd x cm(2)) and HepG2 cells was developed to mimic the gut-liver interactions. This system was used to investigate the effects of raw and fermented barley 13-glucans (RBG and FBG) on lipid metabolism by directly interacting with IEC. Both RBG and FBG significantly and consistently reduced the lipid droplets and triacylglycerol levels in monoculture and coculture of HepG2 overloaded with oleic acid. Notably, FBG significantly and distinctly elevated PPAR alpha (p < 0.05) and PPAR alpha-responsive ACOX-1 (p < 0.01) gene expressions, promoting lipid degradation in cocultured HepG2. Moreover, the metabolomics analyses revealed that FBG had a unique impact on extracellular metabolites, among them, the differential metabolite thiomorpholine 3-carboxylate was significantly and strongly correlated with PPAR alpha (r = -0.68, p < 0.01) and ACOX-1 (r = - 0.76, p < 0.01) expression levels. Taken together, our findings suggest that FBG-mediated gut-liver interactions play a key role in its lipid-lowering effects that are superior to those of RBG. These results support the application of Lactiplantibacillus fermentation for improving hypolipidemic outcomes.