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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Dietary Sulfur Amino Acid Supplementation Reduces Small Bowel Thiol/Disulfide Redox State and Stimulates Ileal Mucosal Growth after Massive Small Bowel Resection in Rats^1,2

³ Graduate Program in Molecular and Systems Pharmacology, Emory University, Atlanta GA 30322 ⁴ Graduate Program in Nutrition and Health Sciences, Emory University, Atlanta GA 30322 ⁵ Department of Medicine, Emory University, Atlanta GA 30322 ⁶ Center for Clinical and Molecular Nutrition, Emory University, Atlanta GA 30322

Following massive small bowel resection in animal models, the remnant intestine undergoes a dynamic growth response termed intestinal adaptation. Cell growth and proliferation are intimately linked to cellular and extracellular thiol/disulfide redox states, as determined by glutathione (GSH) and GSH disulfide (GSSG) (the major cellular redox system in tissues), and cysteine (Cys) and its disulfide cystine (CySS) (the major cellular redox system in plasma), respectively. The study was designed to determine whether dietary supplementation with sulfur amino acids (SAA) leads to a greater reduction in thiol/disulfide redox state in plasma and small bowel and colonic mucosa and alters gut mucosal growth in an established rat model of short bowel syndrome (SBS). Adult rats underwent 80% jejunal-ileal resection (RX) or small bowel transection (surgical control) and were pair-fed either isonitrogenous, isocaloric SAA-adequate (control) or SAA-supplemented diets (218% increase vs. control diet). Plasma and gut mucosal samples were obtained after 7 d and analyzed for Cys, CySS, GSH, and GSSG concentrations by HPLC. Redox status (E_h) of the Cys/CySS and GSH/GSSG couples were calculated using the Nernst equation. SAA supplementation led to a greater reduction in E_h Cys/CySS in jejunal and ileal mucosa of resected rats compared with controls. Resected SAA-supplemented rats showed increased ileal adaptation (increased full-thickness wet weight, DNA, and protein content compared with RX control-fed rats; increased mucosal crypt depth and villus height compared with all other study groups). These data suggest that SAA supplementation has a trophic effect on ileal adaptation after massive small bowel resection in rats. This finding may have translational relevance as a therapeutic strategy in human SBS.

^* To whom correspondence should be addressed. E-mail: tzieg01{at}emory.edu.

Manuscript received 13 February 2009. Initial review completed 13 March 2009. Revision accepted 29 September 2009.