Lactobacillus casei-derived postbiotics inhibited digestion of triglycerides, glycerol phospholipids and sterol lipids via allosteric regulation of BSSL, PTL and PLA2 to prevent obesity: perspectives on deep learning integrated multi-omics

Abstract

The anti-obesity potential of probiotics has been widely reported, however their utilization in high-risk patients and potential adverse reactions have led researchers to focus their attention on postbiotics. Herein, pseudo-targeted lipidomics linked with deep learning-based metabolomics was utilized to dynamically characterize the postbiotic potential of heat-inactivated Lactobacillus casei JCM1134 supplementation after a high-fat diet in treating obesity. MG (ranged from 423.0 ± 1.4 mg L⁻¹ to 331.45 ± 2.3 mg L⁻¹), LPC (ranged from 13.1 ± 0.08 mg L⁻¹ to 10.2 ± 0.1 mg L⁻¹) and Cho (ranged from 9.0 ± 0.3 mg L⁻¹ to 5.7 ± 0.2 mg L⁻¹) in intestinal digestive products were significantly decreased, indicating that the digestion of lipid was inhibited. 8-C-glucosylorobol, from Lactobacillus casei, was confirmed from quantitative results and molecular simulation calculations to inhibit the transformation of TG, DG, and ChE through weakening hydrogen bonds between enzymes and substrates and reducing the binding energy. Pristimerin and 2,4-quinolinediol can effectively reduce the hydrogen bonding force between PC and phospholipase A2, which were related to the obstruction of phosphatidylcholine digestion. This research deepened the understanding of the mechanism underlying the inactivated probiotics affecting lipid digestion, establishing the critical groundwork for clinical application of probiotics in inhibiting obesity.