Accurately quantifying activated immune system energy requirements in vivo is difficult, but a better understanding may advance strategies to maximize animal productivity. Study objectives were to ...estimate whole-body glucose utilization following an i.v. endotoxin challenge. Lactating Holstein cows were jugular catheterized and assigned 1 of 3 bolus treatments: control (CON; 5 mL of saline; n = 6), lipopolysaccharide (LPS)-administered (LPS-C; 1.5 μg/kg of body weight; Escherichia coli 055:B5; n = 6), and LPS + euglycemic clamp (LPS-Eu; 1.5 μg/kg of body weight; 50% glucose solution infusion; n = 6). After LPS administration, blood glucose was determined every 10 min and glucose infusion rates were adjusted in LPS-Eu cows to maintain euglycemia for 720 min. Blood samples were obtained 180, 360, 540, and 720 min postbolus for further analysis. Cows were milked 360 and 720 min postbolus. Blood glucose was increased 84% in LPS-administered cows for up to 150 min postbolus; thereafter, circulating glucose was decreased 30% in LPS-C relative to LPS-Eu and CON cows. Mild hyperthermia (+0.5°C) occurred between 30 and 90 min postbolus in LPS-administered relative to CON cows; thereafter, rectal temperature did not differ between treatments. Milk yield and lactose percentage were decreased 80 and 11%, respectively, in LPS-administered relative to CON cows. Circulating insulin was increased 4 fold and nonesterified fatty acids, β-hydroxybutyrate, and ionized Ca were decreased ∼50% in LPS-administered compared with CON cows. Plasma l-lactate, haptoglobin, and serum amyloid A increased ∼160, 260, and 75%, respectively, in LPS-administered relative to CON cows. Overall, LPS-binding protein was increased 87% in LPS-administered relative to CON cows; however, at 720 min, it was decreased 25% in LPS-Eu compared with LPS-C cows. White blood cell count decreased ∼90% in LPS-administered cows at 180 min and progressively increased to ∼50% of CON values by 720 min. Total glucose deficit during the 720 min following LPS administration was calculated as the decrease in the amount of glucose required to synthesize milk (due to the decrease in milk yield relative to prebolus levels) plus the amount of glucose infused to maintain euglycemia (in LPS-Eu cows only) and was 461, 1,259, and 1,553 g for CON, LPS-C, and LPS-Eu cows, respectively. Our data indicate an acutely activated immune system uses >1 kg of glucose within 720 min and maintaining euglycemia did not rescue milk synthesis.
Objectives were to evaluate the effects of Bacillus subtilis PB6 (BSP) on gastrointestinal tract permeability, metabolism, inflammation, and production parameters in periparturient Holstein cows. ...Multiparous cows (n = 48) were stratified by previous 305-d mature equivalent milk yield and parity and assigned to 1 of 2 top-dressed dietary treatments 21 d before expected calving through 63 DIM: (1) control (CON; 13 g/d calcium carbonate; n = 24) or (2) BSP (13 g/d BSP; CLOSTAT, Kemin Industries, Des Moines, IA; n = 24). Gastrointestinal tract permeability was evaluated in vivo using the oral paracellular marker chromium (Cr)-EDTA. Effects of treatment, time, and treatment × time were assessed using PROC MIXED of SAS version 9.4 (SAS Institute Inc.). Prepartum dry matter intake (DMI) was unaffected by treatment; however, BSP supplementation decreased postpartum DMI relative to CON (0.7 kg). Milk yield, energy-corrected milk (ECM), fat-corrected milk (FCM), and solids-corrected milk (SCM) increased in BSP cows compared with CON (1.6, 1.8, 1.6, and 1.5 kg, respectively). Decreased DMI and increased production collectively improved feed efficiency of milk yield, ECM, FCM, and SCM for BSP cows (6, 5, 5, and 5%, respectively). No treatment differences were observed for concentrations of milk fat, protein, total solids, somatic cell count, somatic cell score, body weight, or body condition score. Milk urea nitrogen concentrations decreased (5%), whereas milk protein and lactose yield increased (5 and 2%, respectively) with BSP supplementation. Prepartum fecal pH did not differ among treatments; conversely, postpartum fecal pH was increased with BSP supplementation (0.09 pH units). Prepartum fecal dry matter percentage, starch, acetic acid, propionic acid, butyric acid, and ethanol did not differ among treatments. Postpartum concentrations of the aforementioned fecal parameters were also unaffected by treatment, but fecal propionic acid concentration was decreased (24%) in BSP cows relative to CON. Circulating glucose, nonesterified fatty acids, l-lactate, and insulin were similar between treatments both pre- and postpartum. Prepartum β-hydroxybutyrate (BHB) did not differ between treatments, but postpartum BSP supplementation decreased (21%) circulating BHB relative to CON. Regardless of treatment, inflammatory markers (serum amyloid A and haptoglobin) peaked immediately following parturition and progressively decreased with time, but this pattern was not influenced by treatment. Postpartum lipopolysaccharide binding protein tended to be decreased on d 3 in BSP relative to CON cows (19%). Neither treatment nor time affected Cr-EDTA area under the curve. In summary, supplementing BSP had no detectable effects prepartum, but increased key postpartum production parameters. Bacillus subtilis PB6 consistently increased postpartum fecal pH and decreased fecal propionate concentrations but did not appear to have an effect on gastrointestinal tract permeability.
Unfavorable weather conditions are one of the largest constraints to maximizing farm animal productivity. Heat stress (HS), in particular, compromises almost every metric of profitability and this is ...especially apparent in the grow-finish and reproductive aspects of the swine industry. Suboptimal production during HS was traditionally thought to result from hypophagia. However, independent of inadequate nutrient consumption, HS affects a plethora of endocrine, physiological, metabolic, circulatory, and immunological variables. Whether these changes are homeorhetic strategies to survive the heat load or are pathological remains unclear, nor is it understood if they temporally occur by coincidence or if they are chronologically causal. However, mounting evidence suggest that the origin of the aforementioned changes lie at the gastrointestinal tract. Heat stress compromises intestinal barrier integrity, and increased appearance of luminal contents in circulation causes local and systemic inflammatory responses. The resulting immune activation is seemingly the epicenter to many, if not most of the negative consequences HS has on reproduction, growth, and lactation. Interestingly, thermoregulatory and production responses to HS are only marginally related. In other words, increased body temperature indices poorly predict decreases in productivity. Further, HS induced malnutrition is also a surprisingly inaccurate predictor of productivity. Thus, selecting animals with a “heat tolerant” phenotype based solely or separately on thermoregulatory capacity or production may not ultimately increase resilience. Describing the physiology and mechanisms that underpin how HS jeopardizes animal performance is critical for developing approaches to ameliorate current production issues and requisite for generating future strategies (genetic, managerial, nutritional, and pharmaceutical) aimed at optimizing animal well-being, and improving the sustainable production of high-quality protein for human consumption.
•Heat stress (HS), compromises every metric of profitability in the grow-finish and reproductive aspects of the swine industry.•Mounting Evidence suggest that the origin of the negative consequences of HS changes lie at the gastrointestinal tract.•Heat stress compromises intestinal barrier integrity, which causes a local and systemic inflammatory response.•Immune activation is the epicenter to many of the negative consequences HS has on reproduction, growth, and lactation.
Study objectives were to evaluate the effects of hindgut acidosis (HGA) on production, metabolism, and inflammation in feed-restricted (FR) dairy cows. Twelve rumen-cannulated cows were enrolled in a ...study with 3 experimental periods (P). During P1 (5 d), baseline data were collected. During P2 (2 d), all cows were FR to 40% of their baseline feed intake. During P3 (4 d), cows remained FR and were assigned to 1 of 2 abomasal infusion treatments: (1) control (FR-CON; 6 L of H2O/d; n = 6) or (2) starch (FR-ST; 4 kg of corn starch + 6 L of H2O/d; n = 6). Respective treatments were partitioned into 4 equal doses (1 kg of corn starch/infusion) and were abomasally infused daily at 0000, 0600, 1200, and 1800 h. All 3 P were analyzed independently and the effects of treatment, time, and treatment × time were assessed using PROC MIXED, and P1 and P2 data were analyzed using the treatments cows were destined to be assigned to during P3. Hallmark production and metabolic responses to feed restriction were observed in both treatments, including decreased milk yield (39%) and energy-corrected milk (32%), circulating glucose (12%), insulin (71%), and increased circulating nonesterified fatty acids (3.2-fold) throughout both P2 and P3, relative to P1. However, despite a marked reduction in fecal pH (0.96 units), the aforementioned metrics were unaltered by HGA. During P3, starch infusions increased circulating β-hydroxybutyrate, with the most pronounced increase occurring on d 2 (81% relative to FR-CON). Further, feed restriction decreased blood urea nitrogen during P2 (17% relative to P1) in both treatments, and this was exacerbated by starch infusions during P3 (31% decrease relative to FR-CON). In contrast to our hypothesis, neither feed restriction nor HGA increased circulating acute-phase proteins (serum amyloid A and lipopolysaccharide binding protein) relative to P1 or FR-CON, respectively. Thus, despite marked reductions in fecal pH, prior feed restriction did not appear to increase the susceptibility to HGA.
Previous stressors and systemic inflammation may increase the intestine's susceptibility to hindgut acidosis (HGA). Therefore, our experimental objectives were to evaluate the effects of isolated HGA ...on metabolism, production, and inflammation in simultaneously immune-activated lactating cows. Twelve rumen-cannulated Holstein cows (118 ± 41 d in milk; 1.7 ± 0.8 parity) were enrolled in a study with 3 experimental periods (P). Baseline data were collected during P1 (5 d). On d 1 of P2 (2 d), all cows received an i.v. lipopolysaccharide (LPS) bolus (0.2 µg/kg of body weight; BW). During P3 (4 d), cows were randomly assigned to 1 of 2 abomasal infusion treatments: (1) control (LPS-CON; 6 L of H2O/d; n = 6) or (2) starch infused (LPS-ST; 4 kg of corn starch + 6 L of H2O/d; n = 6). Treatments were allocated into 4 equal doses (1.5 L of H2O or 1 kg of starch and 1.5 L of H2O, respectively) and administered at 0000, 0600, 1200, and 1800 h daily. Additionally, both treatments received i.v. LPS on d 1 and 3 of P3 (0.8 and 1.6 µg/kg of BW, respectively) to maintain an inflamed state. Effects of treatment, time, and their interaction were assessed. Repeated LPS administration initiated and maintained an immune-activated state, as indicated by increased circulating white blood cells (WBC), serum amyloid A (SAA), and LPS-binding protein (LBP) during P2 and P3 (29%, 3-fold, and 50% relative to P1, respectively) for both abomasal infusion treatments. Regardless of abomasal treatment, milk yield and dry matter intake were decreased throughout P2 and P3 but with lesser severity following each LPS challenge (54, 44, and 37%, and 49, 42, and 40% relative to baseline on d 1 of P2, d 1 and d 3 of P3, respectively). As expected, starch infusions markedly decreased fecal pH (5.56 at nadir vs. 6.57 during P1) and increased P3 fecal starch relative to LPS-CON (23.7 vs. 2.4% of dry matter). Neither LPS nor starch infusions altered circulating glucose, insulin, nonesterified fatty acids, or β-hydroxybutyrate, although LPS-ST cows had decreased blood urea nitrogen throughout P3 (16% relative to LPS-CON). Despite the striking reduction in fecal pH, HGA had no additional effect on circulating WBC, SAA, or LBP. Thus, in previously immune-activated dairy cows, HGA did not augment the inflammatory state, as indicated by a lack of perturbations in production, metabolism, and inflammatory biomarkers.
Heat-stress-induced inflammation may be ameliorated by antioxidant supplementation due to the purported effects of increased production of reactive oxygen species or oxidative stress on the ...gastrointestinal tract barrier. Thus, study objectives were to evaluate whether antioxidant supplementation AGRADO Plus 2.0 (AP); EW Nutrition affects metabolism and inflammatory biomarkers in heat-stressed lactating dairy cows. Thirty-two mid-lactation multiparous Holstein cows were assigned to 1 of 4 dietary-environmental treatments: (1) thermoneutral (TN) conditions and fed a control diet (TN-CON; n = 8), (2) TN and fed a diet with AP (10 g antioxidant; n = 8), (3) heat stress (HS) and fed a control diet (HS-CON; n = 8), or (4) HS and fed a diet with AP (HS-AP; n = 8). The trial consisted of a 23-d prefeeding phase and 2 experimental periods (P). Respective dietary treatments were top-dressed starting on d 1 of the prefeeding period and continued daily throughout the duration of the experiment. During P1 (4 d), baseline data were collected. During P2 (7 d), HS was artificially induced using an electric heat blanket (Thermotex Therapy Systems Ltd.). During P2, the effects of treatment, day, and treatment-by-day interaction were assessed using PROC MIXED of SAS (SAS Institute Inc.). Heat stress (treatments 3 and 4) increased rectal, vaginal, and skin temperatures (1.2°C, 1.1°C, and 2.0°C, respectively) and respiration rate (33 breaths per minute) relative to TN cows. As expected, HS decreased dry matter intake, milk yield, and energy-corrected milk yield (32%, 28%, and 28% from d 4 to 7, respectively) relative to TN. There were no effects of AP on body temperature indices or production. Milk fat, protein, and lactose concentrations remained unaltered by HS or AP; however, milk urea nitrogen was increased during HS regardless of AP supplementation (26% relative to TN). Circulating glucose remained unchanged by HS, AP, or time. Additionally, HS decreased circulating glucagon (29% from d 3 to 7 relative to TN), but there was no additional effect of AP. There was a tendency for nonesterified fatty acid concentrations to be increased in HS-AP cows throughout P2 (60% relative to TN-CON), whereas it remained similar in all other treatments. Blood urea nitrogen increased for both HS treatments from d 1 to 3 before steadily decreasing from d 5 to 7, with the overall increase being most pronounced in HS-CON cows (27% relative to TN-CON). Further, supplementing AP decreased blood urea nitrogen in HS-AP on d 3 relative to HS-CON (15%). Circulating serum amyloid A tended to be and lipopolysaccharide binding protein was increased by HS, but neither acute-phase protein was affected by AP. Overall, AP supplementation appeared to marginally alter metabolism but did not meaningfully alter inflammation during HS.
Postruminal intestinal barrier dysfunction caused by excessive hindgut fermentation may be a source of peripheral inflammation in dairy cattle. Therefore, the study objectives were to evaluate the ...effects of isolated hindgut acidosis on metabolism, inflammation, and production in lactating dairy cows. Five rumen-cannulated lactating Holstein cows (32.6 ± 7.2 kg/d of milk yield, 242 ± 108 d in milk; 642 ± 99 kg of body weight; 1.8 ± 1.0 parity) were enrolled in a study with 2 experimental periods (P). During P1 (4 d), cows were fed ad libitum a standard lactating cow diet (26% starch dry matter) and baseline data were collected. During P2 (7 d), all cows were fed the same diet ad libitum and abomasally infused with 4 kg/d of pure corn starch (1 kg of corn starch + 1.25 L of H2O/infusion at 0600, 1200, 1800, and 0000 h). Effects of time (hour relative to the first infusion or day) relative to P1 were evaluated using PROC MIXED in SAS (version 9.4; SAS Institute Inc.). Infusing starch markedly reduced fecal pH (5.84 vs. 6.76) and increased fecal starch (2.2 to 9.6% of dry matter) relative to baseline. During P2, milk yield, milk components, energy-corrected milk yield, and voluntary dry matter intake remained unchanged. At 14 h, plasma insulin and β-hydroxybutyrate increased (2.4-fold and 53%, respectively), whereas circulating glucose concentrations remained unaltered. Furthermore, blood urea nitrogen increased at 2 h (23%) before promptly decreasing below baseline at 14 h (13%). Nonesterified fatty acids tended to decrease from 2 to 26 h (40%). Circulating white blood cells and neutrophils increased on d 4 (36 and 73%, respectively) and somatic cell count increased on d 5 (4.8-fold). However, circulating serum amyloid A and lipopolysaccharide-binding protein concentrations were unaffected by starch infusions. Despite minor changes in postabsorptive energetics and leukocyte dynamics, abomasal starch infusions and the subsequent hindgut acidosis had little or no meaningful effects on biomarkers of immune activation or production variables.
Hindgut acidosis (HGA) may cause or contribute to the inflammatory state of transition dairy cows by compromising the intestinal barrier. Previous experiments isolating the effects of HGA on ...inflammatory metrics have generated inconsistent results, which may be explained by acclimation to low- versus high-starch diets. Thus, study objectives were to evaluate the effects of HGA in cows acclimated to a high-fiber diet. Ten rumen-cannulated Holstein cows (38 ± 5 kg/d milk yield; 243 ± 62 d in milk; 1.6 ± 1.1 parity; 663 ± 57 kg of body weight) were enrolled in a study with 2 experimental periods (P). Before P1, all cows were acclimated to a high-fiber, low-starch diet (50% neutral detergent fiber, 15% starch) for 17 d. During P1 (4 d), baseline data were collected for use as covariates. During P2 (7 d), cows were assigned to 1 of 2 abomasal infusion treatments: (1) control (CON; 1.5 L of H2O/infusion; n = 4) or (2) starch infused (ST; 1 kg of corn starch + 1.5 L of H2O/infusion; n = 6). All cows were infused with their respective treatments every 6 h daily at 0000, 0600, 1200, and 1800 h, such that ST cows received a total of 4 kg of corn starch/d. Starch infusions successfully induced HGA, as indicated by a marked decrease in fecal pH (1.2 units) relative to CON. However, in contrast to our assumptions, infusing starch had no deleterious effects on milk yield, energy-corrected milk, or voluntary dry matter intake during P2. Milk protein, lactose, their yields, fat yield, and somatic cell score remained unaffected by starch infusions, whereas milk fat content and urea nitrogen were decreased in ST relative to CON (8 and 17%, respectively). Overall, circulating glucose and β-hydroxybutyrate concentrations remained similar between treatments, but starch infusions decreased nonesterified fatty acids on d 3 relative to CON. Blood urea nitrogen decreased throughout P2 in ST (38%) relative to CON. In contrast to our hypothesis, HGA did not alter circulating serum amyloid A or lipopolysaccharide binding protein, nor did it affect rectal temperature. In summary, HGA moderately altered metabolism but did not affect production or elicit an inflammatory response in lactating dairy cows previously acclimated to a high-fiber diet.
The objective of this study was to evaluate the effects of supplementing a Saccharomyces cerevisiae fermentation product (SCFP) on body temperature indices, metabolism, acute phase protein response, ...and production variables during heat stress (HS). Twenty multiparous lactating Holstein cows (body weight = 675 ± 12 kg; days in milk = 144 ± 5; and parity = 2.3 ± 0.1) were used in an experiment conducted in 2 replicates (10 cows/replicate). Cows were randomly assigned to 1 of 2 dietary treatments: control diet (CON; n = 10) or the CON diet supplemented with 19 g/d of SCFP (n = 10; NutriTek, Diamond V, Cedar Rapids, IA). Cows were fed their respective diets for 21 d before initiation of the study. The experiment consisted of 2 periods: thermoneutral (period 1; P1) and heat stress (period 2; P2). During P1 (4 d), cows were fed ad libitum and housed in thermoneutral conditions for collecting baseline data. During P2 (7 d), HS was artificially induced using an electric heat blanket (EHB; Thermotex Therapy Systems Ltd., Calgary, AB, Canada). Cows were fitted with the EHB for the entirety of P2. Rectal temperature, respiration rate, and skin temperature were obtained twice daily (0600 and 1800 h) during both periods. Overall, HS increased rectal temperature, skin temperature, and respiration rate (1.4°C, 4.8°C, and 54 breaths/min, respectively) relative to P1, but no dietary treatment differences were detected. Compared with P1, HS decreased dry matter intake and milk yield (36 and 26%, respectively), and the reductions were similar between dietary treatments. Relative to P1, HS increased milk fat content and milk urea nitrogen (17 and 30%, respectively) and decreased milk protein and lactose contents (7 and 1.4%, respectively). Overall, HS increased (52%) plasma cortisol concentrations of CON, but circulating cortisol did not change in SCFP-fed cows. Heat stress increased circulating lipopolysaccharide binding protein and serum amyloid A (SAA; 2- and 4-fold, respectively), and SCFP supplementation tended to decrease peak SAA (∼33%) relative to CON cows. Overall, although HS did not influence circulating white blood cells and neutrophils, SCFP increased circulating white blood cells and neutrophils by 9 and 26%, respectively, over CON in P2. In conclusion, HS initiated an acute phase protein response and feeding SCFP blunted the cortisol and SAA concentrations and altered some key leukocyte dynamics during HS.
Cashew nut shell extract (CNSE) is a byproduct of the cashew nut industry, containing bioactive compounds that alter rumen fermentation patterns. Therefore, study objectives were to evaluate the ...effects of CNSE (59% anacardic acid and 18% cardol) on production, rumen fermentation variables, metabolism, and inflammation in transition dairy cows. A total of 51 multiparous Holstein cows were used in a randomized design and assigned to treatment based on their previous 305-d mature equivalent milk and parity. Cows were assigned to 1 of 2 treatments 21 d before expected calving: (1) CON (control diet; n = 17) or (2) CNSE-5.0 (control diet and 5.0 g/d CNSE granule containing 50% CNSE; n = 34). Following parturition, 17 cows (preselected at initial treatment assignment) from the CNSE-5.0 treatment were reallocated into a third treatment group: CNSE-2.5 (control diet and 2.5 g/d CNSE granule; n = 17), resulting in 3 total treatments postpartum: (1) CON, (2) CNSE-2.5, and (3) CNSE-5.0. Prepartum rumen pH was unaltered by treatment; however, postpartum rumen pH was increased (0.31 units) in CNSE cows relative to CON. Prepartum rumen ammonia N concentration tended to be decreased (34%) in CNSE-5.0 cows compared with CON, and there tended to be a quadratic effect on postpartum ammonia N, as it was decreased in CNSE-2.5 compared with CON and CNSE-5.0. Prepartum dry matter intake (DMI) was unaffected by treatment; however, postpartum DMI was increased (8%) in CNSE cows relative to CON. No treatment differences were observed in pre- or postpartum digestibility measurements. Milk and protein yields from cows fed CNSE tended to be increased (6% and 7%, respectively) relative to CON. No treatment differences were detected for energy-corrected milk, feed efficiency, body weight, body condition score, energy balance, milk composition, milk urea nitrogen, or somatic cell count. Prepartum fecal pH decreased (0.12 units) in CNSE-5.0 cows relative to CON cows but was similar between treatments postpartum. Supplementing CNSE did not affect prepartum glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHB), or insulin. However, prepartum circulating blood urea nitrogen tended to be decreased and glucagon was decreased in CNSE-5.0 cows compared with CON (9 and 20%, respectively). Additionally, CNSE supplementation decreased glucose and insulin concentrations postpartum relative to CON cows (6% and 20%, respectively). Quadratic effects were detected for postpartum circulating NEFA and BHB such that their levels were increased in CNSE-2.5 cows relative to CON and CNSE-5.0. Pre- and postpartum circulating serum amyloid A, lipopolysaccharide-binding protein, and haptoglobin were unaffected by treatment. Overall, CNSE influenced some key rumen fermentation variables, altered postabsorptive metabolism, and increased production parameters in transition dairy cows.
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