|KVIDERA, S. - Iowa State University|
|DICKSON, M. - Iowa State University|
|ABUAJAMIEH, M. - Iowa State University|
|SNIDER, D. - Iowa State University|
|SANZ FERNANDEZ, M. - Iowa State University|
|KEATING, A. - Iowa State University|
|GORDON, P. - Iowa State University|
|GREEN, H. - Elanco Animal Health, Inc|
|SCHOENBERG, K. - Elanco Animal Health, Inc|
|BAUMGARD, L. - Iowa State University|
Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/26/2017
Publication Date: 5/1/2017
Citation: Kvidera, S.K., Dickson, M.J., Abuajamieh, M., Snider, D.B., Sanz Fernandez, M.V., Johnson, J.S., Keating, A.F., Gordon, P.J., Green, H.B., Schoenberg, K.M., Baumgard, L.H. 2017. Intentionally induced intestinal barrier dysfunction causes inflammation, affects metabolism, and reduces productivity in lactating Holstein cows. Journal of Dairy Science. 100(5):4113-4127. doi: 10.3168/jds.2016-12349.
Interpretive Summary: The intestinal barrier serves a dual role in absorbing nutrients while also preventing infiltration of unwanted compounds and molecules into the body. In livestock species such as dairy cattle, the importance of barrier function is enhanced due to both the size of the intestinal tract and the potential toxin exposure due to fermentation in the rumen. Therefore, the study objectives were to determine the direct impact of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. The hypothesis was that intestinal tract barrier dysfunction in otherwise healthy animals would directly impact productivity, metabolic variables, and inflammatory indices. To test this hypothesis, gamma-secretase inhibitor was given to dairy cows via an intravenous solution twice daily for 7 days to reduce intestinal barrier integrity. A second group of control dairy cows were given saline solution intravenously for 7 days. Control cows were pair-fed to treatment animal levels to eliminate the confounding effects of dissimilar nutrient intake on intestinal integrity. As a result of the treatments, intestinal morphology was negatively altered, productivity was reduced, and biomarkers of metabolic health were impacted in gamma-secretase inhibitor treated cows compared to controls. In summary, intentionally compromising intestinal barrier function directly increased inflammation and reduced productivity in otherwise healthy dairy cows and this provides evidence that intestinal health can directly impact the health and well-being of livestock species.
Technical Abstract: Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 days in milk) were enrolled in two experimental periods. Period 1 (P1; 5 d) served as the baseline for period 2 (P2; 7 d) during which cows received one of two i.v. treatments twice daily: 1) sterile saline or 2) gamma-secretase inhibitor (GSI; 1.5 mg/kg body weight). GSI reduces intestinal barrier function via inhibiting crypt cell differentiation into enterocytes. During P2, control cows receiving sterile saline were pair-fed (PF) to the GSI-treated cows and all cows were euthanized at the end of P2. Administering GSI increased goblet cell area ~200, 70, and 28% in jejunum, ileum, and colon, respectively. In the jejunum, GSI-treated cows had increased crypt depth and reduced villus height, villus height-to-crypt depth ratio, cell proliferation, and mucosal surface area. Plasma lipopolysaccharide binding protein increased with time, and tended to be increased ~40% in GSI-treated cows relative to PF-controls on d 5-7. Circulating haptoglobin and serum amyloid A concentrations increased (> 500 and > 4 fold, respectively) similarly in both treatments. Administering GSI progressively reduced dry matter intake (~65%) and, by design, the pattern and magnitude of decreased nutrient intake was similar in PF-controls. A similar progressive decrease (~40%) in milk yield occurred in both treatments, and there were no treatment effects detected on milk components. Cows treated with GSI tended to have increased plasma insulin (~70%) and decreased circulating non-esterified fatty acids (~30%) compared to PF cows. For both treatments, plasma glucose decreased with time while ß-hydroxybutyrate progressively increased. Liver triglycerides increased 125% at sacrifice in both treatments. There were no differences in liver weight, liver moisture, or body weight change. In summary, intentionally compromising intestinal barrier function caused inflammation, altered metabolism and markedly reduced feed intake and milk yield. Further, we have demonstrated progressive feed reduction appears to cause leaky gut and inflammation.