Effect of partial exchange of lactose with fat in milk replacer on performance and blood metabolites of Holstein calves.

The objective of this study was to determine the effect of dietary energy source (fat vs. carbohydrate) in calf milk replacer (MR) on growth performance parameters and feed intake in rearing calves. In a randomized complete block design, 68 Holstein calves [40 females and 28 males; (mean ± SD) body weight (BW): 43.7 ± 1.43 kg] were assigned to 17 blocks of 4 calves based on birth date and parity of the dam. Within each block, calves were randomly assigned to 1 of 2 treatments: a high-lactose MR (HL; 17% fat; 44% lactose; n = 34), or a high-fat MR (HF; 23% fat; 37% lactose; n = 34). Lactose was exchanged for fat on a weight per weight basis, resulting in a 6% difference in metabolizable energy density per kilogram of MR. The feeding plan started with 6 L/d for 7 d, then 8 L/d for 35 d, 6 L/d for 7 d, and finally, 4 L/d for 7 d. Milk replacer allowances were offered in 2 meals per day at 140 g/L. Measurements included daily MR, starter and straw intakes, weekly BW, and blood metabolites, including nonesterified fatty acids (NEFA) and glucose, on wk 4, 6, 8, and 10. Increasing fat at the expense of lactose did not affect MR intake or solid feed intake during the preweaning and weaning periods. However, HF calves tended to consume more solid feed than HL calves during the postweaning period (2.63 ± 0.08 vs. 2.52 ± 0.08 kg/d). Additionally, average daily gain (HF = 0.78 ± 0.02, HL = 0.77 ± 0.02 kg/d) and final BW (HF = 98.8 ± 1.53, HL = 97.7 ± 1.57 kg) were not affected by MR composition. Nevertheless, NEFA concentration was higher in HF calves than in HL calves (0.21 ± 0.01 vs. 0.17 ± 0.01 mmol/L), and glucose concentration was higher in HF calves (6.52 ± 0.23 vs. 5.86 ± 0.23 mmol/L). Under the conditions of this study, HF calves consumed similar amounts of solid feed and grew comparably to the HL calves; however, the isonitrogenous replacement of lactose by fat had evident metabolic effects, such as increased blood NEFA and glucose concentrations.

Effect of partial exchange of lactose with fat in milk replacer on ad libitum feed intake and performance in dairy calves.

Compared with Holstein whole milk, commercial milk replacers (MR) for calves deliver relatively high levels of lactose and low levels of fat, and protein levels are rather comparable, resulting in a lower energy density and energy-to-protein ratio of the diet. Thus, the objective of this study was to determine the effects of partially exchanging lactose with fat in MR on voluntary feed intake, growth performance, and feeding behavior. Thirty-two male Holstein calves (2.1 ± 0.16 d of age, 46.4 ± 0.77 kg of body weight; BW) were assigned to 16 blocks of 2 calves per block based on arrival date and serum IgG. Within each block, calves were randomly assigned to 2 treatments: a high-lactose MR (HL; 17% fat; 44% lactose), or a high-fat MR (HF; 23% fat; 37% lactose). Lactose was exchanged by fat on a weight per weight basis, resulting in a 6% difference in metabolizable energy density per kilogram of MR. The experiment was divided into 3 phases: preweaning (P1; 0-35 d), weaning (P2; 36-56 d), and postweaning (P3; 57-84 d). For the first 2 wk of P1, calves were individually housed, fed their respective MR ad libitum through teat buckets, and provided access to water. At 14.2 ± 0.5 d of age, calves were group-housed (4 blocks/pen, 8 calves) and housed in group pens for the remainder of the study. In the group pens, calves were fed ad libitum MR, starter feed, chopped wheat straw, and water via automated feeders. During P2, calves were gradually weaned until complete milk withdrawal by 57 d and then monitored until 84 d (P3). Measurements included daily intakes and feeding behavior (rewarded and unrewarded visits), weekly BW and body measurements, and biweekly blood samples. Increasing fat content at the expense of lactose decreased MR intake during P1 by 15% (HL = 1.32 ± 0.04; HF = 1.17 ± 0.04 kg of dry matter per day), whereas total starter intake was not affected by MR composition. Once MR was restricted during P2, HL calves were reported to have more unrewarded visits to the automatic milk feeder than HF calves (11.9 ± 0.95 vs. 8.4 ± 1.03 visits/d, respectively). Crude protein intake was higher for HL calves during P1 (352.1 ± 11.2 vs. 319.6 ± 11.6 g/d), which was attributed to the higher intake of MR during that period, and metabolizable energy intake and protein-to-energy ratio remained comparable between treatments. Plasma cholesterol and nonesterified fatty acids levels were higher in HF calves as a consequence of the diet. Nevertheless, final BW (84 d) did not differ between treatments. Overall, calves fed ad libitum seemed to regulate their intake of MR based on its energy density, without significant effects on solid feed intake and overall growth.

Hypertonic milk replacers increase gastrointestinal permeability in healthy dairy calves.

Hypertonic milk replacers are commonly used in animal production systems and their effect on the gastrointestinal system of young animals is insufficiently studied. Total lactose inclusion or its partial replacement with dextrose increases intestinal osmotic pressure, which may compromise gastrointestinal barrier function. In this experiment, we investigated the effect of increased osmolality of calf milk replacer (CMR) on gastrointestinal permeability in 30 Holstein Friesian (n = 17) or crossbred (n = 13) bull calves. The osmolality of CMR increased as result of a gradual replacement of lactose by monosaccharides (dextrose and galactose). Calves were acquired from dairy farms that followed a standardized protocol for colostrum management, including 3 feedings of colostrum in the first 24 h. Calves were then transported to the research facility between 0 and 3 d of age, fed a milk replacer with 0% dextrose twice daily for the first 2 wk of age, and subsequently exposed to their respective treatments from 3 until 7 wk of age. Meal size was 3.2 L at 3 wk of age and increased to 3.5 L at 7 wk of age. No solids were provided throughout the study and calves had ad libitum access to water. Treatments included 4 levels of dextrose inclusion (replacing lactose): 0% (L1, n = 5), 13.3% (L2, n = 5), 26.7% (L3, n = 5), and 40% (L4, n = 5) and an additional treatment (G+D, n = 10) that included 20% galactose and 20% dextrose and matched the galactose supply of L1 and the osmolality of L4. Carbohydrates were exchanged based on hexose equivalents. Across treatments, the estimated osmolality ranged from 439 (L1) to 611 mOsm/kg (L4 and G+D). Gastrointestinal permeability was assessed by fractional urinary recovery of indigestible markers (lactulose, d-mannitol, and Cr-EDTA) delivered as a single dose at 3 and 7 wk of age. Marker recoveries were expressed as percentage of oral dose and assessed in 6-h and 24-h quantitative urinary collections. Increasing the osmolality of the CMR linearly increased urinary Cr-EDTA and lactulose recoveries at 3 and 7 wk of age. Lactulose and Cr-EDTA recoveries did not differ between G+D and L4, suggesting that the source of monosaccharide (dextrose and galactose) in CMR had no effect on gastrointestinal permeability. The observed increase in gastrointestinal permeability to large molecules (Cr-EDTA and lactulose) with increased osmolality suggests that hypertonic CMR may compromise gastrointestinal barrier function.

Nutrient supply alters transcriptome regulation in adipose tissue of pre-weaning Holstein calves.

Performance of dairy cows can be influenced by early life nutrient supply. Adipose tissue is diet sensitive and an important component in that process as it is involved in the regulation of energetic, reproductive and immunological functions. However, it is not clear how early life nutrition alters the molecular regulation of adipose tissue in calves and potentially adult individuals. This study aimed at determining how differences in pre-weaning nutrient supply alter gene expression profiles and physiology in omental adipose tissue. A total of 12 female Holstein calves were fed two levels of milk replacer supply: a restricted amount of 11.72 MJ of metabolizable energy (ME) intake per day (n = 6) or an enhanced amount of 1.26 MJ ME intake per kg of metabolic body weight (BW0.75), resulting in supply from 17.58 to 35.17 MJ ME intake per day (n = 6). All calves had ad libitum access to a commercial calf starter and water. Analysis of the transcriptome profiles at 54 ± 2 days of age revealed that a total of 396 out of 19,968 genes were differentially expressed (DE) between groups (p < 0.001, FDR < 0.1). The directional expression of DE genes through Ingenuity Pathway Analysis showed that an enhanced nutrient supply alters adipose tissue physiology of pre-weaned calves. Several biological functions were increased (Z-score > +2), including Lipid Metabolism (Fatty Acid Metabolism), Cell Cycle (Entry into Interphase, Interphase, Mitosis and Cell Cycle Progression), Cellular Assembly and Organization (Cytoskeleton Formation and Cytoplasm Development) and Molecular Transport (Transport of Carboxylic Acid). These changes were potentially orchestrated by the activation/inhibition of 17 upstream regulators genes. Our findings indicate that adipose tissue of calves under an enhanced nutrient supply is physiologically distinct from restricted calves due to an increased development/expansion rate and also a higher metabolic activity through increased fatty acid metabolism.

Diurnal variation of NMR based blood metabolites in calves fed a high plane of milk replacer: a pilot study.

BACKGROUND: Blood profiles have been used to monitor herd health status, diagnose disorders, and predict the risk of diseases in cattle and calves. Characterizing plasma metabolites in dairy calves could provide further insight into daily metabolic variations and the mechanisms that lead to metabolic diseases. In addition, by understanding physiological ranges of plasma metabolites relative to meal and the time of feeding in healthy animals, veterinarians can accurately diagnose abnormalities with a blood test. For diagnostic purposes, nuclear magnetic resonance (NMR) spectroscopy shows promise as a new and reliable method to determine a large number of blood metabolites simultaneously. RESULTS: Results demonstrated that the concentration of specific metabolites in plasma (i.e., lysine, isoleucine, leucine, tyrosine, glutamine, creatine, and 1-methylhistidine) fluctuated around meal times, while others (i.e., glutamic acid, methanol, formic acid, and acetic acid) maintained a stable temporal concentration. In addition to temporal changes in concentration, results also characterized differences for overall plasma metabolite concentrations; for example, methionine had the lowest (38 µM) while glutamine had the highest concentration (239 µM) amongst plasma AA. This is the first report describing how the plasma metabolome changes during 24-h period in young calves fed an elevated plane of milk replacer twice daily. CONCLUSIONS: Data from this pilot study will help to establish reference standards for future metabolic diagnostics in dairy calves. In addition, this pilot study illustrated that feeding milk replacer may influence plasma metabolite concentrations. With the rapid implementation of blood metabolomics in monitoring animal health, it is then important to consider the time of feeding during the day when interpreting metabolomics analysis results.

From pre- to postweaning: Transformation of the young calf's gastrointestinal tract.

The ruminant gastrointestinal tract (GIT) faces the challenge of protecting the host from luminal contents and pathogens, while supporting the absorption and metabolism of nutrients for growth and maintenance. The GIT of the calf in early life undergoes some of the most rapid microbial and structural changes documented in nature, and these adaptations in GIT function make the young calf susceptible to GIT diseases and disorders. Despite these challenges, the calf's GIT has a certain degree of plasticity and can sense nutrient supply and respond to bioactive ingredients. Calf GIT research has historically focused on the transition during weaning and characterizing ruminal papillae development using microscopy and digesta metabolite responses. Through the use of new molecular-based approaches, we have recently shown that delaying the age of weaning and providing a step-down weaning protocol is associated with a more gradual shift in ruminal microbiota to a postweaned state. In addition to ruminal adaptations during weaning, nutrient flow to the lower gut changes dramatically during weaning, coinciding with a wide array of structural and microbiological changes. Structural and gene expression changes suggest that the lower gut of the dairy calf undergoes alterations that may reduce barrier function when solid feeds are consumed. More recently, in vivo data revealed that the weaning transition increases total gut permeability of the calf. Interestingly, the lower gut may be able to communicate with the forestomach, meaning that a nutrient can be sensed in the lower gut and cause subsequent adaptations in the forestomach. An improved understanding of how diet, microbiota, and functional ingredients interact to affect growth and barrier function of the intestinal tract would greatly benefit the dairy calf industry. A mechanistic understanding of such adaptations would also aid in the formulation of specific management regimens and provision of functional ingredients required to characterize and enhance gut function in young calves.

A Mechanistic Model of Intermittent Gastric Emptying and Glucose-Insulin Dynamics following a Meal Containing Milk Components.

To support decision-making around diet selection choices to manage glycemia following a meal, a novel mechanistic model of intermittent gastric emptying and plasma glucose-insulin dynamics was developed. Model development was guided by postprandial timecourses of plasma glucose, insulin and the gastric emptying marker acetaminophen in infant calves fed meals of 2 or 4 L milk replacer. Assigning a fast, slow or zero first-order gastric emptying rate to each interval between plasma samples fit acetaminophen curves with prediction errors equal to 9% of the mean observed acetaminophen concentration. Those gastric emptying parameters were applied to glucose appearance in conjunction with minimal models of glucose disposal and insulin dynamics to describe postprandial glycemia and insulinemia. The final model contains 20 parameters, 8 of which can be obtained by direct measurement and 12 by fitting to observations. The minimal model of intestinal glucose delivery contains 2 gastric emptying parameters and a third parameter describing the time lag between emptying and appearance of glucose in plasma. Sensitivity analysis of the aggregate model revealed that gastric emptying rate influences area under the plasma insulin curve but has little effect on area under the plasma glucose curve. This result indicates that pancreatic responsiveness is influenced by gastric emptying rate as a consequence of the quasi-exponential relationship between plasma glucose concentration and pancreatic insulin release. The fitted aggregate model was able to reproduce the multiple postprandial rises and falls in plasma glucose concentration observed in calves consuming a normal-sized meal containing milk components.

Fermentation in the small intestine contributes substantially to intestinal starch disappearance in calves.

BACKGROUND: The proportion of starch disappearing from the small intestinal lumen is generally lower in ruminants than in monogastric animals, and there are indications that the starch digestion capacity in ruminants is limited. OBJECTIVES: Milk-fed calves were used to study the rate-limiting enzyme in starch hydrolysis and to quantify starch fermentation in ruminants. METHODS: Forty male Holstein-Friesian calves were fed milk replacer containing either lactose (control) or 1 of 4 corn starch products. The following starch products differed in the enzyme ratios required for their complete hydrolysis to glucose: gelatinized starch [α-amylase and (iso)maltase], maltodextrin [(iso)maltase and α-amylase], maltodextrin with α-1,6-branching (isomaltase, maltase, and α-amylase), and maltose (maltase). In the adaptation period, calves were stepwise exposed to an increasing dose of the starch product for 14 wk to allow maximal adaptation of all enzyme systems involved. In the experimental period, apparent total tract and ileal starch product disappearance, total tract starch product fermentation, and α-amylase, maltase, and isomaltase activities were determined at 18% inclusion of the starch product. RESULTS: Maltase and isomaltase activities in the brush border did not increase for any of the starch product treatments. Luminal α-amylase activity was lower in the proximal (3.9 ± 3.2 and 2.7 ± 1.7 U/mg Co for control and starch product calves, respectively) but greater in the distal small intestine of starch-fed calves than in control calves (0.0 ± 0.0 and 6.4 ± 1.5 U/mg Co for control and starch product calves, respectively; means ± SEs for control and means ± pooled SEMs for starch product treatments). Apparent ileal (61.6% ± 6.3%) and total tract (99.1% ± 0.4%) starch product disappearance did not differ between starch product treatments, suggesting that maltase activity limits starch digestion in ruminants. Total tract starch product fermentation averaged 414 ± 43 g/d, corresponding to 89% of intake, of which half was fermented before the terminal ileum, regardless of starch product treatment. CONCLUSION: Fermentation, rather than enzymatic digestion, is the main reason for small intestinal starch disappearance in milk-fed calves.

Urea recycling contributes to nitrogen retention in calves fed milk replacer and low-protein solid feed.

Urea recycling, with urea originating from catabolism of amino acids and hepatic detoxification of ammonia, is particularly relevant for ruminant animals, in which microbial protein contributes substantially to the metabolizable protein supply. However, the quantitative contribution of urea recycling to protein anabolism in calves during the transition from preruminants (milk-fed calves) to ruminants [solid feed (SF)-fed calves] is unknown. The aim of this study was to quantify urea recycling in milk-fed calves when provided with low-protein SF. Forty-eight calves [164 ± 1.6 kg body weight (BW)] were assigned to 1 of 4 SF levels [0, 9, 18, and 27 g of dry matter (DM) SF · kg BW(-0.75) · d⁻¹] provided in addition to an identical amount of milk replacer. Urea recycling was quantified after a 24-h intravenous infusion of [¹5N2]urea by analyzing urea isotopomers in 68-h fecal and urinary collections. Real-time qPCR was used to measure gene expression levels of bovine urea transporter B (bUTB) and aquaglyceroporin-3 and aquaglyceroporin-7 in rumen wall tissues. For every incremental gram of DM SF intake (g DM · kg(0.75)), nitrogen intake increased by 0.70 g, and nitrogen retention increased by 0.55 g (P < 0.01). Of this increase in nitrogen retention, 19% could be directly explained by urea recycling. Additionally, part of the observed increase in nitrogen retention could be explained by the extra protein provided by the SF and likely by a greater efficiency of postabsorptive use of nitrogen for gain. Ruminal bUTB abundance increased (P < 0.01) with SF provision. Aquaglyceroporin-3 expression increased (P < 0.01) with SF intake, but aquaglyceroporin-7 expression did not. We conclude that in addition to the increase in digested nitrogen, urea recycling contributes to the observed increase in nitrogen retention with increasing SF intake in milk-fed calves. Furthermore, ruminal bUTB and aquaglyceroporin-3 expression are upregulated with SF intake, which might be associated with urea recycling.