Gut adaptations in rat models of short bowel syndrome (SBS) and chronic alcohol exposure

The intestine demonstrates a remarkable capacity for morphological and functional adaptation under a wide variety of pathological conditions, such as the massive small bowel resection (mSBR) and alcoholism. mSBR is a surgical procedure for treatment of various intestinal disorders, leading to a cluster of clinical complications known as short bowel syndrome (SBS), such as malabsorption and barrier dysfunction. In search of potential novel therapies for SBS, we first assessed the effects of redox factor glutathione (GSH) and gut-trophic factor glutamine (GLN) on gut adaptive growth. Both GSH and GLN have been suggested in literature for stimulation of mucosal growth. Our experiments with specific inhibition of GSH synthesis in SBS rats revealed that GSH content and its redox status does not affect the adaptive growth in small intestine but stimulate both basal and adaptive growth in colon. The results indicate the complexity of redox regulation of cell growth in vivo. Dietary GLN supplementation significantly enhanced the adaptive growth in the residual small intestine in SIBS rats. Next, we investigated the gut barrier function alteration by measuring the bacterial translocation and its serum markers, luminal secretory IgA (sIgA), and expression of tight junction proteins. Our data demonstrate that bacterial translocation increases after mSBR with a concomitant increase a luminal sIgA, indicating adaptation of immunological barrier, which is likely in response to the bacterial invasion. Dietary supplementation of GLN enhanced the sIgA increase and inhibited bacterial translocation in post-mSBR rats, suggesting sIgA as a mechanism for GLN effect in preventing bacterial translocation. Finally, we investigated the intestinal adaptation in a rat model of chronic alcohol ingestion. Our data show that rat intestine has a site-specific response of antioxidant GSH to alcohol treatment, i.e., GSH content was increased in jejunum, unaltered in ileum, and decreased in colon. Such changes occur whilst another low molecular weight thiol, cysteine, was globally reduced in mucosa, suggesting the presence of oxidative stress. Thus, the induction of GSH in jejunal mucosa may be an adaptive mechanism in response to alcohol-induced oxidative stress. Overall, our study provided multi-faceted view of gut adaptations and the potential approaches for enhancing the adaptations.