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

Author
item Connor, Erin
item Kahl, Stanislaw
item Elsasser, Theodore
item Baldwin, Ransom
item Fayer, Ronald
item Santin, Monica
item Sample, Gregory
item Clover, Christina

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2012
Publication Date: 2/26/2013
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.