Intentionally induced intestinal barrier dysfunction causes inflammation, affects metabolism, and reduces productivity in lactating Holstein cows.
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 d in milk) were enrolled in 2 experimental periods. Period 1 (5 d) served as the baseline for period 2 (7 d), during which cows received 1 of 2 i.v. treatments twice per day: sterile saline or a gamma-secretase inhibitor (GSI; 1.5 mg/kg of body weight). Gamma-secretase inhibitors reduce intestinal barrier function by inhibiting crypt cell differentiation into absorptive enterocytes. During period 2, control cows receiving sterile saline were pair-fed (PF) to the GSI-treated cows, and all cows were killed at the end of period 2. Administering GSI increased goblet cell area 218, 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 42% in GSI-treated cows relative to PF controls on d 5 to 7. Circulating haptoglobin and serum amyloid A concentrations increased (585- and 4.4-fold, respectively) similarly in both treatments. Administering GSI progressively reduced dry matter intake (66%) and, by design, the pattern and magnitude of decreased nutrient intake was similar in PF controls. A similar progressive decrease (42%) in milk yield occurred in both treatments, but we observed no treatment effects on milk components. Cows treated with GSI tended to have increased plasma insulin (68%) and decreased circulating nonesterified fatty acids (29%) compared with PF cows. For both treatments, plasma glucose decreased with time while β-hydroxybutyrate progressively increased. Liver triglycerides increased 221% from period 1 to sacrifice in both treatments. No differences were detected in liver weight, liver moisture, or body weight change. Intentionally compromising intestinal barrier function caused inflammation, altered metabolism, and markedly reduced feed intake and milk yield. Further, we demonstrated that progressive feed reduction appeared to cause leaky gut and inflammation.
Department of Animal Science, Iowa State University, Ames 50011.
S K
SK
Kvidera
Department of Animal Science, Iowa State University, Ames 50011.
M J
MJ
Dickson
Department of Animal Science, Iowa State University, Ames 50011.
M
M
Abuajamieh
Department of Animal Science, Iowa State University, Ames 50011.
D B
DB
Snider
Department of Animal Science, Iowa State University, Ames 50011.
M V Sanz
MVS
Fernandez
Department of Animal Science, Iowa State University, Ames 50011.
J S
JS
Johnson
Department of Animal Science, Iowa State University, Ames 50011.
A F
AF
Keating
College of Veterinary Medicine, Iowa State University, Ames 50011.
P J
PJ
Gorden
Elanco Animal Health, Greenfield, IN 46140.
H B
HB
Green
Elanco Animal Health, Greenfield, IN 46140.
K M
KM
Schoenberg
Department of Animal Science, Iowa State University, Ames 50011. Electronic address: baumgard@iastate.edu.
L H
LH
Baumgard
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000821:Animal Feed; D000818:Animals; D002417:Cattle; D004032:Diet / Q000662:veterinary; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007249:Inflammation / Q000378:metabolism; D007774:Lactation; D008892:Milk / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D020155:3-Hydroxybutyric Acid
inflammation; insulin; intestinal integrity; lipopolysaccharide