Differential Regulation of Intestinal Glucose Transporters SGLT1 and GLUT2 by Lactobacillaceae-Derived Heat-Killed Probiotics and Cell-Free Probiotic Supernatants.

Background/Objectives: Although paraprobiotics and postbiotics may beneficially affect glucose metabolism, their direct influence on intestinal glucose transporters remains poorly understood. This study investigated the in vitro effects of selected heat-killed Lactobacillaceae strains and cell-free supernatants from their viable counterparts on sodium-driven glucose cotransporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) expression and basolateral glucose accumulation. Methods: Experiments were performed using non-carcinogenic porcine-derived enterocytes (CLAB) and human epithelial colorectal adenocarcinoma cells (Caco-2; ATCC HTB-37). SGLT1 and GLUT2 gene and protein expression, as well as basolateral glucose concentration after a 6-h incubation, were assessed. Results: Heat-killed probiotics and cell-free probiotic supernatants generally increased SGLT1 protein expression in both cell models, except for heat-killed Lactobacillus acidophilus. In contrast, GLUT2 modulation differed between cell models and treatments. In CLAB cells, GLUT2 protein levels were generally reduced, particularly following exposure to cell-free probiotic supernatants, whereas responses in Caco-2 cells were less consistent. Treatment-dependent changes in basolateral glucose concentration and 6-h net basolateral glucose accumulation were also observed, with significant effects for selected heat-killed strains in CLAB cells. Conclusions: Lactobacillaceae-derived heat-killed preparations and cell-free supernatants may differentially modulate intestinal glucose transporter expression in a strain- and cell-model-dependent manner. However, changes in transporter expression and basolateral glucose accumulation do not establish a transporter-specific glucose flux or mechanism. Further mechanistic studies using complementary intestinal models are required to clarify these effects and their translational relevance.