Fan_2023_Mol.Nutr.Food.Res__e2300336

SCOPE: The antiobesity function of probiotics has been declared, while the application in high-risk patients and coding side effect has focused attention to postbiotics. This investigation profiles the mechanism of postbiotics affecting lipid digestion at molecular level, and establishes a momentous foundation for the clinical application of postbiotics in obesity suppression. METHODS AND RESULTS: An operational framework for butter digestion is constructed to collect the digests in the intestine at 0, 40, 80, and 120 min with various postbiotics supplement. A total of 227 lipids and 414 metabolites are detected by pseudo-targeted lipidomics integrated with the long short-term memory-based metabolomics, and the triacylglycerol (TG, from 134.1 to 184.7 mg kg(-1) ) and diacylglycerol (DG, from 4.2 to 8.4 mg kg(-1) ) are identified as significantly different lipids with or without postbiotics supplement. A total of eight substances related to the inhibition of gastric lipase and pancreatic lipase are screened through the molecular simulation computation in silicon and enzymatic reaction kinetics, and thus curtailing the bioaccessibility of lipids. CONCLUSIONS: Lactobacillus casei JCM1134-derived postbiotics propel the structure of lipase to aggregate by increasing the alpha-helix, and thus hampering the digestion of triglycerides through noncompetitive inhibition.