Glucagon-like peptide 2 therapy reduces negative effects of diarrhea on calf gut

Authors: Connor, Erin; Kahl, Stanislaw; Elsasser, Theodore; Baldwin, Ransom - Randy; Fayer, Ronald; Santin-Duran, Monica; Sample, Gregory; Clover, Christina - Chris

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2012
Publication Date: 2/26/2013
Publication URL: http://handle.nal.usda.gov/10113/56568
Citation: Connor, E.E., Kahl, S., Elsasser, T.H., Baldwin, R.L., Fayer, R., Santin, M., Sample, G.L., Clover, C.M. 2013. Glucagon-like peptide 2 therapy reduces negative effects of diarrhea on calf gut. Journal of Dairy Science. 96(3):1793-1802.

Interpretive Summary: Diarrhea can cause intestinal damage, reduce nutrient absorption and animal growth rate, and may have long-term effects on animal production. For instance, recently it was found that the number of days that a heifer calf had diarrhea during the first four months of life had a significant negative effect on 305-d mature equivalent milk production and actual milk, protein, and fat production in the first-lactation. The current work uses experimentally induced coccidiosis as a model to evaluate the use of glucagon-like peptide 2 (GLP-2) as a therapy to improve nutrient uptake and reduce intestinal damage caused by diarrhea in neonatal Holstein bull calves. Results suggest promise for reducing intestinal damage related to diarrhea through GLP-2 therapy.

Technical Abstract: Damage to the intestinal epithelium caused by diarrhea reduces nutrient absorption and growth rate, and may have long-term effects on the young animal. Glucagon-like peptide 2 (GLP-2) is an intestinotropic hormone that improves gut integrity and nutrient absorption, and has antioxidant effects in the gut. Our objective was to determine whether GLP-2 treatment of calves with diarrhea caused by coccidiosis in the first month of life can improve intestinal absorptive capacity and function. Holstein bull calves (n = 19) were assigned to 1 of 4 treatment groups: 1) infected with Eimeria bovis, GLP-2-treated (Eim-GLP2; n = 5); 2) uninfected, GLP-2-treated (Con-GLP2; n = 4); 3) infected with Eimeria bovis, buffer-treated (Eim-Buffer; n = 5); and 4) uninfected, buffer-treated (Con-Buffer; n = 5). Infected calves received 2 ' 105 sporulated Eimeria bovis oocysts suspended in milk replacer on d 0 of the study. On d 18, calves in the GLP2 groups received a subcutaneous injection of 50 µg/kg BW of bovine GLP-2 in sodium carbonate/bicarbonate buffer twice daily for 10 d, and calves in the Buffer groups received an equivalent volume of buffer only. D-xylose intestinal absorptive capacity of each calf was measured on d 0, 17, and 27. On d 28, calves were sacrificed 2 h after injection of 5-bromo-2'-deoxyuridine (BrdU). Intestinal tissues were measured and harvested for evaluation of villus height, crypt depth, and BrdU and nitrotyrosine immunostaining. There was no GLP-2 treatment by Eimeria infection interaction for any parameter measured. Large intestinal weight was increased by Eimeria infection and GLP-2 treatment. Treatment with GLP-2 also increased small intestinal weight and tended to increase BrdU labeling in jejunum. No treatment effects were detected for villus height, crypt depth, or villus height:crypt depth ratio in any segment of the small intestine. Similarly, no treatment effects on intestinal D-xylose absorptive capacity were detected. Protein tyrosine nitration in ileum was increased by approximately 3.8 fold by Eimeria infection, and GLP-2 treatment tended to reduce nitrotyrosine immunostaining in ileum. These results suggest that GLP-2 treatment may improve intestinal epithelial growth in neonatal calves. Although no evidence of improved intestinal absorptive capacity of calves was demonstrated with GLP-2 treatment, GLP-2 therapy may reduce the detrimental effects of protein tyrosine nitration in the gut of calves with diarrhea caused by coccidiosis.