TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis

Inflammatory bowel disease (IBD) has a close association with transketolase (TKT) that links glycolysis and the pentose phosphate pathway (PPP). However, how TKT functions in the intestinal epithelium remains to be elucidated. To address this question, we specifically delete TKT in intestinal epithelial cells (IECs). IEC TKT-deficient mice are growth retarded and suffer from spontaneous colitis. TKT ablation brings about striking alterations of the intestine, including extensive mucosal erosion, aberrant tight junctions, impaired barrier function, and increased inflammatory cell infiltration. Mechanistically, TKT deficiency significantly accumulates PPP metabolites and decreases glycolytic metabolites, thereby reducing ATP production, which results in excessive apoptosis and defective intestinal barrier. Therefore, our data demonstrate that TKT serves as an essential guardian of intestinal integrity and barrier function as well as a potential therapeutic target for intestinal disorders.

Automated summary

Depletion of TKT in intestinal epithelial cells leads to growth retardation and spontaneous colitis in mice, along with extensive mucosal erosion, aberrant tight junctions, impaired barrier function, and increased inflammatory cell infiltration in the intestine. This is due to the accumulation of PPP metabolites and reduction of glycolytic metabolites, resulting in decreased ATP production, excessive apoptosis, and defective intestinal barrier. Thus, TKT plays a crucial role in maintaining intestinal integrity and barrier function, suggesting it could be a potential therapeutic target for intestinal disorders.