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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #376212

Research Project: Microbiota and Nutritional Health

Location: Children's Nutrition Research Center

Title: Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

item GROVER, MADHUSUDAN - Mayo Clinic
item DASARI, SURENDRA - Mayo Clinic
item BERNARD, CHERYL - Mayo Clinic
item YATES, KATHERINE - Johns Hopkins School Of Public Health
item PASRICHA, PANKAJ - Johns Hopkins University School Of Medicine
item SAROSIEK, IRENE - Texas Tech University Health Science Center
item MCCALLUM, RICHARD - Texas Tech University Health Science Center
item KOCH, KENNETH - Wake Forest University
item ABELL, THOMAS - University Of Louisville
item KUO, BRADEN - Massachusetts General Hospital
item SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)
item GIBBONS, SIMON - Mayo Clinic
item MCKENZIE, TRAVIS - Mayo Clinic
item KELLOGG, TODD - Mayo Clinic
item KENDRICK, MICHAEL - Mayo Clinic
item TONASCIA, JAMES - Johns Hopkins School Of Public Health
item HAMILTON, FRANK - National Institute Of Diabetes And Digestive And Kidney Diseases
item PARKMAN, HENRY - Temple University
item FARRUGIA, GIANRICO - Mayo Clinic

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/27/2019
Publication Date: 11/1/2019
Citation: Grover, M., Dasari, S., Bernard, C.E., Chikkamenahalli, L.L., Yates, K.P., Pasricha, P.J., Sarosiek, I., McCallum, R., Koch, K.L., Abell, T.L., Kuo, B., Shulman, R.J., Gibbons, S.J., McKenzie, T.J., Kellogg, T.A., Kendrick, M.L., Tonascia, J., Hamilton, F.A., Parkman, H.P., Farrugia, G. 2019. Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis. American Journal of Physiology - Gastrointestinal and Liver Physiology. 317(5):G716-G726.

Interpretive Summary: Slow stomach emptying can be a crippling disorder affecting children and adults. Because it causes nausea and vomiting, it can be associated with malnutrition. The cause is poorly understood. A recent study by researchers in Houston, in collaboration with the NIH Gastroparesis Consortium, used a cutting edge technique called proteomics to detect changes in the types of proteins found in the stomach of individuals with slow stomach emptying as compared to healthy people. The results showed abnormal immune function in those with slow stomach emptying. These results will help lead to new treatment strategies for addressing this debilitating disorder which may involve nutritional intervention.

Technical Abstract: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, "Role of Macrophages, Fibroblasts and Endothelial Cells" was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 x 10-9; IG FDR = 6.3 x 10-12]. In DG, properdin expression correlated with GCSI bloating (r = -0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C- type, and complement C2 correlated with 4 h gastric retention (r = -0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis.