8th Annual BMRP Investigator Meeting - Abstract
Improvement of Gastrointestinal Barrier Function and Morbidity by Restriction of Sulfur-Containing Amino Acids in Crohn’s Disease Patients
James M. Mullin1,2,a, Mary Carmen Valenzano1, Yvette Mercer1, Giancarlo Mercogliano2, Matthew Astroff3, Marcia Costello4, James J. Thornton2, Keith Kearney2, Kevin Wolov2, Owen Tully2, Benjamin Ngo2, Melissa Morgan2 and Christopher Farrell2
1Lankenau Institute for Medical Research; 2Division of Gastroenterology, Lankenau Hospital (Wynnewood, Pennsylvania, U.S.A.); 3Division of Gastroenterology, Paoli Hospital (Pennsylvania, U.S.A.); 4Villanova University School of Nursing (Pennsylvania, U.S.A)
Prior work by our group in an epithelial cell culture model has shown that 80% reduction of extracellular methionine alters and improves tight junction (TJ) structure and barrier function. Similar reduction of methionine, like caloric restriction, has forestalled age-related disease significantly in various animal models. Given the link of Crohn’s disease (CD) and gastrointestinal TJ leak, we hypothesized that dietary reduction of methionine might improve GI barrier function and morbidity in CD. 10 CD patients to date have been placed for 4 weeks on a low-methionine diet (30% of normal methionine intake) supplemented with Hominex due to its low-protein nature. Although CDAI scores improve while on diet, lactulose/mannitol (L/M) permeability ratios increase on diet, relative to pre-diet and post-diet measurements. BUN decreases on diet but other serology is unaffected. Plasma methionine levels decrease very little on diet (5%) due perhaps to hydrolysis of labile protein stores in kidney and liver, in response to decreased intake of a specific amino acid.
aPrincipal Investigator