Auswirkungen der Restaurativen Proktokolektomie auf den Glutaminstoffwechsel bei Patienten mit Colitis Ulcerosa und Patienten mit Familiärer Polyposis Coli

Abstract

Background: Restorative proctocolectomy as the surgical treatment of choice for patients with ulcerative colitis (UC) and those with familial adenomatous polyposis coli (FAP) imposes an essential change of function on the terminal ileal mucosa. Glutamine is one of the major nutrients for the small-bowel mucosa; it is metabolized into glutamate and subsequently alanine in the human enterocyte. In a prospective clinical trial we compared glutamine distribution in patients with ulcerative colitis to that in patients with familial adenomatous polyposis coli before and after restorative proctocolectomy, as well as in healthy individuals. Method: Concentrations of glutamine, glutamate and alanine were measured pre- and postoperatively in the terminal ileal mucosa, pouch mucosa, skeletal muscle (in median mmol/kg wet weight) and venous blood (in median mmol/l plasma) of patients undergoing total colectomy and construction of an ileoanal pouch for ulcerative colitis (UC, n = 27) or familial adenomatous polyposis coli (FAP; n = 17). Healthy individuals served as controls for skeletal muscle glutamine concentration. Results: Glutamine concentration in the skeletal muscle of healthy individuals, patients with UC and patients with FAP before IPAA did not show a significant difference (9.56, 8.55, 8.11, p = 0.82), nor did the glutamine sequence profile in terminal ileal mucosa and blood of UC and FAP patients, respectively. After IPAA, glutamine concentrations in UC patients decreased significantly in skeletal muscle (8.55, 7.24, p = 0.034). In the mucosa, glutamine increased nonsignificantly (0.70, 0.88, p = 0.10), while glutamate and alanine concentrations increased significantly (2.72, 4.13, p < 0.001; 0.76, 1.36, p = 0.003). In plasma, glutamine concentrations increased significantly (0.52, 0.58, p = 0.017). In FAP patients, glutamine levels did not change in skeletal muscle (7.14, 7.08, p = 0.31) after IPAA. In mucosa, glutamine levels increased non-significantly (0.64, 0.80, p = 0.73), whereas glutamate (2.18, 3.96, p< 0.001) and alanine (0.86, 1.20, p = 0.011) increased significantly. In plasma, glutamine levels remained unaltered (0.57, 0.56, p = 0.59). After IPAA, glutamine concentration in the pouch mucosa was significantly higher in UC than in FAP patients (p = 0.029). Conclusion: Glutamine concentrations in the store skeletal muscle of UC patients and FAP patients before surgical therapy were equal to that in healthy individuals. Restorative proctocolectomy resulted in changes in the glutamine sequence profile in ileal mucosa of both groups of patients, but resulted in significant decrease of glutamine concentrations in the store skeletal muscle only in UC patients, indicating redistribution and increased consumption of glutamine by the ileal pouch mucosa. Investigations into possible associations between characteristics of glutamine metabolism and the occurrence of pouchitis in patients with UC are required.