Disruption of the transsulfuration pathway by acute kidney injury causes intestinal damage

Acute kidney injury (AKI) impairs intestinal function through oxidative stress. The transsulfuration pathway is essential for sulfur amino acid metabolism and antioxidant defense through glutathione biosynthesis. This study investigated how AKI caused intestinal injury and the mechanisms involved. AKI was induced in Sprague-Dawley rats through kidney ischemia (45 min)-reperfusion (24 h). AKI decreased intestinal glutathione (antioxidant) levels and compromised intestinal barrier function. Glutathione biosynthesis in mammals requires cysteine made through the reverse transsulfuration pathway, catalyzed by cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). AKI decreased the expression of these enzymes in intestinal epithelium. AKI also altered gut microbiota composition and the expression of bacterial enzymes in the forward transsulfuration pathway, which could disrupt intestinal antioxidant defense. The inhibition of this pathway in gut epithelial cells reduced glutathione levels and tight junction protein expression. These results suggest that the disruption of the transsulfuration pathway impairs antioxidant defense, leading to intestinal barrier damage and dysbiosis in AKI.