|WALL, EMMA - Pancosma Sa|
|BRAVO, DAVIS - Pancosma Sa|
|Baldwin, Ransom - Randy|
|WALKER, MICHAEL - Former ARS Employee|
Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2016
Publication Date: 1/26/2017
Citation: Connor, E.E., Wall, E.H., Bravo, D.M., Clover, C.M., Elsasser, T.H., Baldwin, R.L., Santin, M., Kahl, S., Vinyard, B.T., Walker, M.P. 2017. Reducing gut effects from Cryptosporidium parvum infection in dairy calves through prophylactic glucagon-like peptide 2 therapy or feeding of an artificial sweetener. Journal of Dairy Science. 100(4):3004-3018.
Interpretive Summary: Glucagon-like peptide 2 (GLP-2) is an intestinal hormone that is released in response to feeding which promotes nutrient uptake by the body. The hormone also functions in maintaining the health and integrity of the intestinal wall, and promotes tissue healing after gut injury. It has been shown by others that consumption of artificial sweeteners causes GLP-2 to be released from specialized cells in the gut. Our laboratory has shown that GLP-2 therapy can reduce gut damage in dairy calves with coccidiosis. Therefore, this study examined whether GLP-2 therapy or feeding of an artificial sweetener to newborn Holstein bull calves beginning 1 week prior to a low-level oral exposure to the coccidian parasite, Cryptosporidium parvum, can prevent or reduce their intestinal damage caused by subsequent infection. Versus untreated infected calves, it was determined that GLP-2 and artificial sweetener treatments had minor benefits including reduced diarrhea, improved intestinal morphology, a reduced plasma indicator of inflammation, and increased intestinal antioxidant enzyme gene expression, all of which may contribute to less intestinal injury during infection.
Technical Abstract: Glucagon-like peptide 2 (GLP-2) therapy was shown previously to reduce inflammation-related gut damage from coccidiosis in dairy calves, and feeding of artificial sweetener stimulates GLP-2 secretion from intestinal L cells. The purpose of this study was to determine whether GLP-2 treatment or artificial sweetener feeding beginning 1 wk prior to an experimental inoculation with the coccidian parasite Cryptosporidium parvum can reduce infection-related intestinal damage in Holstein bull calves. Newborn calves were assigned to 1 of 4 treatment groups of 6 calves each including non-infected controls injected s.c. every 12 h with control buffer (CON), infected controls injected s.c. every 12 h with control buffer (INF), infected and injected s.c. every 12 h with 50 µg/kg BW GLP-2 (GLP2), and infected, injected s.c. every 12 h with control buffer, and supplemented in the diet with Sucram at 400 mg/kg DM of milk replacer (SUC). Treatments were initiated on D 1, and the INF, GLP2, and SUC groups were orally dosed on D 8 with 12,500 C. parvum oocysts. Fecal scores were recorded daily, plasma was collected on D 1, 8, 12, 15, and 18 to evaluate markers of inflammation, and fecal samples were collected on D 1, 8, and every other day thereafter to determine the presence of oocysts. Calves were sacrificed on D 18 for collection of intestinal tissues and histological and gene expression analyses. Infected calves in groups INF, GLP2, and SUC exhibited an increase in diarrhea severity versus the CON group, but SUC and GLP2 groups had reduced diarrhea severity versus the INF group. On D 15, plasma serum amyloid A was elevated in all infected groups relative to the CON group, but serum amyloid A levels were reduced with GLP2 and SUC treatments, which reached normal levels by D18. Expression of MARVELD2 and GPX2 mRNA was increased in intestinal mucosa of INF calves, but was eliminated in SUC and GLP groups, suggesting that the treatments may protect against changes in intestinal integrity and damage induced by infection. Lastly, ileal villous height was maintained at normal levels in GLP2 calves, the SUC group had reduced apoptosis and cell proliferation in intestinal crypts, and both groups exhibited increased intestinal mass-to-length ratio. Our findings suggest that GLP-2 or Sucram treatments administered prior to a low-level C. parvum exposure may contribute to less intestinal injury in response to infection.