Intentionally induced intestinal barrier dysfunction causes inflammation, affects metabolism, and reduces productivity in lactating Holstein cows

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 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.

Responses to rumen-protected choline in transition cows do not depend on prepartum body condition

“…In fact, Mohsen et al (2011) observed that supplemental RPC increased coefficients of total-tract nutrient digestibility, which increased the calculated energy content of the diet and enhanced efficiency of yield of 4% FCM per unit of DMI. Moreover, it has been suggested that the decline in DMI around parturition may have detrimental effects on the gastrointestinal barrier (Kvidera et al, 2017). Changes in gut permeability could potentially facilitate the entry of antigens into the bloodstream and elicit an inflammatory response [i.e., induce an acute phase response (Kvidera et al, 2017)].…”

“…Moreover, it has been suggested that the decline in DMI around parturition may have detrimental effects on the gastrointestinal barrier (Kvidera et al, 2017). Changes in gut permeability could potentially facilitate the entry of antigens into the bloodstream and elicit an inflammatory response [i.e., induce an acute phase response (Kvidera et al, 2017)]. Zenobi et al (2018b) subjected cows to feed restriction in an attempt to mimic the negative energy balance observed in early lactation.…”

Mucosal Immune System of Cattle

“…2; Figs. [3][4][5][6][7][8][9]. Secretory IgA (sIgA) is produced when dimeric IgA is secreted by the plasma cells in the LP and is transported to the mucosal surface of the epithelial cell.…”

“…6). 9 This leakiness also occurs in the respiratory and reproductive tract. ME have important immune regulatory functions that affect the mucous barrier, tight junctions, and the innate and adaptive immune cells in the LP.…”

Influence of Mushroom Polysaccharide, Nano-Copper, Copper Loaded Chitosan, and Lysozyme on Intestinal Barrier and Immunity of LPS-mediated Yellow-Feathered Chickens

“…Intestinal inflammatory response has been shown to cause intestinal epithelium dysfunction, and reduce the absorption of nutrients in animals, through altering the permeability of the natural barrier [35]. The reduction of intestinal inflammatory response may contribute to improved growth performance [36].…”