FIGURE 10.

Schematic overview of metabolic regulation in Caco-2 cells cultured with C. difficile. First, C. difficile causes inhibition of energy metabolism, including glycolysis and the TCA cycle, along with downregulation of the electron transport chain in Caco-2 cells during the early stage of infection. Mitochondrial dysfunction leads to ROS production, and in response, Caco-2 cells upregulate the glutathione-dependent antioxidant system. Second, ER stress in Caco-2 cells caused by CDI causes the accumulation of nonfunctional proteins (unfolded and misfolded proteins). Caco-2 cells degrade nonfunctional proteins through the ubiquitin proteasomal pathway and reduce protein synthesis. Finally, C. difficile induces damage to cell junctions, including tight junctions and adherens junctions, in Caco-2 cells. In response, Caco-2 cells upregulate syndecan-4 to maintain intestinal epithelial barrier function. ETC, electron transfer chain; ER, endoplasmic reticulum.