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.     

Effect of feed restriction on reproductive and metabolic hormones in dairy cows

The objective of this trial was to evaluate the effects of feed restriction (FR) on serum glucose, nonesterified fatty acids, progesterone (P4), insulin, and milk production in dairy cows. Eight multiparous Holstein cows, 114 ± 14 d pregnant and 685 ± 39 kg of body weight, were randomly assigned to a replicated 4 × 4 Latin square design with 14-d periods. During the first 8 d of each period, cows in all treatments were fed for ad libitum feed intake. Beginning on d 9 of each period, cows received 1 of 4 treatments: ad libitum (AL), 25% feed restriction (25FR), 50% feed restriction (50FR), and 50% of TMR replaced with wheat straw (50ST). Daily feed allowance was divided into 3 equal portions allocated every 8 h with jugular blood samples collected immediately before each feeding through d 14. In addition, on d 12 of each period, blood samples were collected before and at 60, 120, 180, 240, 300, 360, 420, and 480 min after morning feeding. The conventional total mixed ration and total mixed ration with straw averaged 15.1 and 10.8%, 32.1 and 50.5%, and 26.8 and 17.0% for concentrations of crude protein, neutral detergent fiber, and starch, respectively. Cows that were feed and energy restricted had reduced dry matter intake, net energy for lactation intake, circulating glucose concentrations, and milk production, but greater body weight and body condition score losses than AL cows. Circulating concentrations of insulin were lower for cows fed 50FR (8.27 μIU/mL) and 50ST (6.24 μIU/mL) compared with cows fed AL (16.65 μIU/mL) and 25FR (11.16 μIU/mL). Furthermore, the greatest plasma nonesterified fatty acids concentration was observed for 50ST (647.7 μEq/L), followed by 50FR (357.5 μEq/L), 25FR (225.3 μEq/L), and AL (156.3 μEq/L). In addition, serum P4 concentration was lower for cows fed AL than cows fed 50ST and 25FR. Thus, FR reduced circulating glucose and insulin but increased P4 concentration, changes that may be positive in reproductive management programs.     

Feed restriction to induce and meloxicam to mitigate potential systemic inflammation in dairy cows before calving

Most dairy cows experience a transient decrease in feed intake in the 1 to 2 wk before calving, which has been associated with systemic inflammation (SI), indicated by increased blood haptoglobin (Hp) concentration. We aimed to characterize the association between prepartum decrease in feed intake and the onset of SI and, if present, the ability of meloxicam (MEL), a non-steroidal anti-inflammatory drug, to mitigate SI. Holstein cows (n = 45) were assigned to control (n = 13), feed restriction (FR) untreated (FR-U; n = 15), and FR treated with MEL (FR-T; n = 17) groups. Daily feed intake was measured from ?22 d from expected parturition until 35 d postpartum. Control cows were fed ad libitum, whereas FR-U and FR-T cows were reduced to 60% of their average intake for 4 consecutive days (?15 to ?12 d from expected calving). The FR-T cows received MEL (0.5 mg/kg of body weight) once daily for 4 consecutive days (?13 to ?10 d from expected calving). Blood samples were collected ?22, ?15, ?14, ?13, ?12, ?10, ?7, ?5, ?3, 0, 1, 3, 5, 7, 15, 22, and 35 d relative to calving to measure serum concentrations of total calcium, total protein, albumin, globulin, cholesterol, urea, glucose, gamma-glutamyl transferase, aspartate aminotransferase, glutamate dehydrogenase, β-hydroxybutyrate, nonesterified fatty acids, Hp, and insulin-like growth factor-1. Serum concentrations of lipopolysaccharide-binding protein were measured ?22, ?15, ?14, ?13, ?12, and ?10 d from expected calving. Simplified glucose tolerance tests were performed on ?15, ?12, ?5, 1, and 5 d relative to calving. Mixed linear regression models were used to assess the effects of FR and MEL on each metabolite. The interaction between treatment group and blood sampling day was forced into each model. All models accounted for body condition score, parity, and the cow as a random effect. Nonesterified fatty acids concentrations in both the FR-U and FR-T groups significantly increased from the second until the last day of FR. Feed restriction increased urea concentrations compared with the control group on ?14 d but decreased urea concentrations on ?10 d from expected calving. Control cows had greater β-hydroxybutyrate concentrations compared with FR cows on 15, 21, and 35 d postpartum. For all other metabolites, no differences were found. This model of FR produced substantial fat mobilization but based on serum Hp and lipopolysaccharide-binding protein concentrations did not generate measurable SI; therefore, we were unable to evaluate the ability of MEL to mitigate SI.     

Effects of hindgut acidosis on production,metabolism, and inflammatory biomarkers in feed-restricted lactating dairy cows

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.     

Peripartum responses of dairy cows to prepartal feeding level and dietary fatty acid source

This experiment was conducted to investigate the effect of feeding level and oilseed supplementation during the close-up dry period on energy balance (EB), hepatic lipidosis, metabolic status, and productivity in early lactation. Seventy-seven Holstein cows were blocked according to parity and expected calving date and then assigned randomly to 1 of 6 treatments in a 2 × 3 factorial allocation with 2 feeding levels: ad libitum (AL) or 30% feed restriction (FR), and 3 dietary fatty acid sources: canola seed, linola seed, or flaxseed at 8% of dietary dry matter (DM), to enrich the rations with oleic, linoleic, or linolenic acids, respectively during the last 4 wk of gestation. After parturition, all cows were fed a common lactation diet. Cows fed AL lost less body weight (−2.9 vs. −6.0%) and body condition score (+0.67 vs. −2.30%), and consequently were in more positive EB (+4.6 vs. −0.3 Mcal) during the prepartum period than cows subjected to FR. Postpartum, FR cows lost less body weight (−9.7 vs. −12.4%) and experienced less severe negative EB (−4.5 vs. −7.0 Mcal) than AL cows. Cows fed AL had higher plasma insulin (6.8 vs. 4.4 μIU/mL) and lower nonesterified fatty acid concentrations (436 vs. 570 mEq/mL) during the close-up period than cows subjected to FR. Cows fed AL tended to have lower liver glycogen content in early lactation than cows subjected to FR (4.4 vs. 2.9 μg/g of DM), but had similar triglyceride content (13.1 ± 1.2 μg/g of DM). Fatty acid source did not influence response variables. In conclusion, eliminating intake depression by FR during the close-up period had positive carryover effects on EB and metabolic status during early lactation, but feeding linoleic and linolenic acids via unprotected oilseeds only had negligible effects on peripartum responses.     

灵菌红素对断奶大鼠肠道发育以及抗氧化能力的影响

为研究灵菌红素对肠道发育以及抗氧化能力的影响,以断奶应激诱导的肠道损伤大鼠为实验动物模型,将30只断奶SD雄性大鼠随机平均分成对照组、低剂量组和高剂量组,对照组大鼠每天灌胃生理盐水,低剂量组和高剂量组大鼠每天分别灌胃剂量为100、200μg/kg的灵菌红素溶液(以体质量计);喂养实验持续14 d后处死实验大鼠并取样;记录大鼠每天的体质量和采食量;称取各组织器官质量,测量小肠和结肠的长度,计算器官指数;采用苏木精-伊红染色方法观察回肠和结肠的形态结构,测量回肠绒毛高度和隐窝深度以及结肠黏膜厚度和杯状细胞数量;检测回肠和结肠组织中总抗氧化能力(total antioxidant capacity,T-AOC)、谷胱甘肽过氧化物酶(glutathione-peroxidase,GHS-Px)、超氧化物歧化酶(superoxide dismutase,SOD)活力和丙二醛的水平。结果表明:高剂量灵菌红素能够显著提高大鼠的体质量、平均日采食量(P0.05),显著增加肝脏、脾脏和胸腺指数(P0.05),显著增加小肠和结肠指数,增加回肠绒毛高度、绒腺比和结肠黏膜厚度(P0.05);显著增加回肠组织中T-AOC、GHS-Px和SOD活力(P0.05),并降低回肠组织中丙二醛含量;显著增加结肠组织中SOD活力(P0.05),降低结肠组织中丙二醛含量。结论:灵菌红素有利于提高断奶大鼠的生长性能,提高回肠和结肠的抗氧化能力,具有缓解断奶应激诱导的大鼠肠道损伤的作用。     

Effects of feeding vitamin A and lactoferrin on epithelium of lymphoid tissues of intestine of neonatal calves

Circulating levels of vitamin A (retinol) and lactoferrin (Lf) are low in calves at birth. Bovine colostrum contains relatively high amounts of vitamin A and Lf, and both substances are intestinally absorbed by neonatal calves. There is evidence that these compounds interact with insulin-like growth factor binding proteins and thus influence the status and effects of insulin-like growth factor. The hypothesis was therefore tested that vitamin A and Lf influence epithelial growth, development, and absorptive capacity of the small and large intestine and modulate intestinal immune tissues (Peyer's patches; PP). Four groups of calves (n = 7 per group) were fed a milk-based formula with or without vitamin A and (or) Lf. Group F received formula (F) only; group F(A) was fed F supplemented with vitamin A; group F(L) was fed F supplemented with Lf, and group F(AL) received F plus vitamin A plus Lf. An additional group of calves (group C; n = 7) served as positive control and was fed colostrum (C) from pooled milk obtained on d 1, 2, and 3 of lactation. Amounts of nutritive components in formula and colostrum were similar. Blood samples were taken to measure vitamin A and Lf, and plasma xylose (added on d 4 to feeds) was measured postprandially for 8 h as a marker of intestinal absorptive capacity. Plasma vitamin A was low at birth and further decreased in groups F and F(L), but increased in groups F(A), F(AL), and C. Plasma Lf was low at birth and transiently increased up to 4 h after the first meal in group C. Xylose absorption was higher in group C than in other groups. Incorporation of 5-bromo-2'-deoxyuridine into DNA (as a measure of cell proliferation rate) was enhanced in intestinal crypts in groups F and F(L) at all intestinal sites. Ileum villus heights of groups F and F(L) were smaller than of groups F(A) and F(AL). Villus height to crypt depth ratios were smaller in F-fed groups (especially in groups F and F(L)) than in C-fed calves in the duodenum and jejunum. Incorporation of 5-bromo-2'-deoxyuridine into colon crypt cells of group F was greater than in groups F(L) and F(A). Sizes of follicles of PP in the ileum were greater in group F(A) than in group F. In the ileum, vitamin A and Lf tended to interact with PP size. In conclusion, feed supplementation of vitamin A and Lf influenced growth of the ileum and colon. Interactions were observed between vitamin A and Lf on epithelial cell maturation, villus growth, and size of follicles in PP of neonatal calves.     

Evaluation of feed restriction and abomasal infusion of resistant starch as models to induce intestinal barrier dysfunction in healthy lactating cows

Intestinal hyperpermeability and subsequent immune activation alters nutrient partitioning and thus, decreases productivity. Developing experimental models of intestinal barrier dysfunction in heathy cows is a prerequisite in identifying nutritional strategies to mitigate it. Six cannulated Holstein cows (mean ± standard deviation, 37 ± 10 kg/d milk yield; 219 ± 97 d in milk; 691 ± 70 kg body weight) were used in a replicated 3 × 3 Latin square design experiment with 21-d periods (16-d wash-out and 5-d challenge) to evaluate either feed restriction or hindgut acidosis as potential models for inducing intestinal hyperpermeability. Cows were randomly assigned to treatment sequence within square and treatment sequences were balanced for carryover effects. Treatments during the challenge were (1) control (CTR; ad libitum feeding); (2) feed restriction (FR; total mixed ration fed at 50% of ad libitum feed intake); and (3) resistant starch (RS; 500 g of resistant starch infused in abomasum once a day as a pulse-dose 30 min before morning feeding). The RS (ActiStar RT 75330, Cargill Inc.) was tapioca starch that was expected to be resistant to enzymatic digestion in the small intestine and highly fermentable in the hindgut. Blood samples were collected 4 h after feeding on d 13 and 14 of the wash-out periods (baseline data used as covariate), and on d 1, 3, and 5 of the challenge periods. Fecal samples were collected 4 and 8 h after the morning feeding on d 14 of the wash-out periods and d 5 of the challenge periods. By design, FR decreased dry matter intake (48%) relative to CTR and RS, and this resulted in marked reductions in milk and 3.5% FCM yields over time, with the most pronounced decrease occurring on d 5 of the challenge (34 and 27%, respectively). Further, FR increased somatic cell count by 115% on d 5 of the challenge relative to CTR and RS. Overall, FR increased nonesterified fatty acids (159 vs. 79 mEq/L) and decreased BHB (8.5 vs. 11.2 mg/dL), but did not change circulating glucose relative to CTR. However, RS had no effect on production or metabolism metrics. Resistant starch decreased fecal pH 8 h after the morning feeding (6.26 vs. 6.81) relative to CTR and FR. Further, RS increased circulating lipopolysaccharide binding protein (4.26 vs. 2.74 µg/mL) compared with FR only on d 1 of the challenge. Resistant starch also increased Hp (1.52 vs. 0.48 µg/mL) compared with CTR, but only on d 5 of the challenge. However, neither RS or FR affected concentrations of serum amyloid A, IL1β, or circulating endotoxin compared with CTR. The lack of consistent responses in inflammatory biomarkers suggests that FR and RS did not meaningfully affect intestinal barrier function. Thus, future research evaluating the effects of hindgut acidosis and FR using more intense insults and direct metrics of intestinal barrier function is warranted.     

Short communication: Ketosis,feed restriction,and an endotoxin challenge do not affect circulating serotonin in lactating dairy cows

Circulating serotonin (5-hydroxytryptamine; 5-HT) appears to be associated with various energetic disorders and hypocalcemia during the transition period. The objective of this study was to evaluate the effects of ketosis, feed restriction (FR), and endotoxin challenge (models in which energetic and calcium metabolism are markedly altered) on circulating 5-HT in lactating Holstein cows. Blood samples were obtained from 3 separate experiments; circulating β-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), and glucose were measured in all 3 experiments, whereas ionized calcium (iCa²⁺) was measured only in the endotoxin challenge. In the ketosis study, blood samples from cows clinically diagnosed with ketosis (n = 9) or classified as healthy (n = 9) were obtained from a commercial dairy farm at d ?7, 3, and 7 relative to calving. Ketosis was diagnosed using a urine-based test starting at 5 d in milk. There was no effect of health status on circulating 5-HT and no association between 5-HT and BHB, NEFA, or glucose; however, 5-HT concentrations progressively decreased following calving. In the FR experiment, mid-lactation cows were either fed ad libitum (n = 3) or restricted to 20% of their ad libitum intake (n = 5) for 5 d. There were no FR effects on circulating 5-HT, nor was FR correlated with energetic metabolites. In the immune activation model, mid-lactation cows were intravenously challenged with either lipopolysaccharide (LPS; 1.5 µg/kg of BW; n = 6) or sterile saline (control; n = 6). Administering LPS decreased (56%) blood iCa²⁺ but had no effect on circulating 5-HT, nor was there a correlation between circulating 5-HT and NEFA, BHB, or iCa²⁺. Circulating 5-HT tended to be positively correlated (r = 0.54) with glucose in Holstein cows administered LPS. In summary, in contrast to expectations, circulating 5-HT was unaffected in models of severely disturbed energetic and Ca²⁺ homeostasis.     

Nutrient demand interacts with forage family to affect digestion responses in dairy cows

Effects of forage family on dry matter intake (DMI), milk production, ruminal pool sizes, digestion and passage kinetics, and chewing activity and the relationship of these effects with preliminary DMI (pDMI), an index of nutrient demand, were evaluated using 13 ruminally and duodenally cannulated Holstein cows in a crossover design with a 14-d preliminary period and two 18-d treatment periods. During the preliminary period, pDMI of individual cows ranged from 19.6 to 29.5 kg/d (mean=25.9 kg/d) and 3.5% fat-corrected milk yield ranged from 24.3 to 60.3 kg/d (mean=42.1 kg/d). Experimental treatments were diets containing either a) alfalfa silage (AL) or b) orchardgrass silage (OG) as the sole forage. Alfalfa and orchardgrass contained 42.3 and 58.2% neutral detergent fiber (NDF) and 22.5 and 11.4% crude protein, respectively. Forage:concentrate ratios were 60:40 and 43:57 for AL and OG, respectively; both diets contained approximately 25% forage NDF and 30% total NDF. Preliminary DMI was determined during the last 4 d of the preliminary period when cows were fed a common diet and used as a covariate. Main effects of forage family and their interaction with pDMI were tested by ANOVA. Forage family and its interaction with pDMI did not affect feed intake, milk yield, or milk composition. The AL diet increased indigestible NDF (iNDF) intake and decreased potentially digestible NDF (pdNDF) intake compared with OG. The AL diet increased ruminal pH, digestion rates of pdNDF and starch, and passage rates of pdNDF and iNDF compared with OG, which affected ruminal digestibility. Passage rate of iNDF was related to pDMI; AL increased iNDF passage rate and OG decreased it as pDMI increased. The AL diet decreased ruminal pool sizes of pdNDF, starch, organic matter, dry matter, and rumen digesta wet weight and volume compared with OG. The AL diet decreased ruminating time per unit of forage NDF consumed compared with OG, indicating that alfalfa provided less physically effective fiber than orchardgrass. The AL diet, but not OG, increased ammonia N, nonammonia nonmicrobial N, and nonammonia N fluxes as pDMI increased. Efficiency of microbial protein synthesis was positively related to pdNDF passage rate for OG, but not AL. The faster rates of digestion and passage for AL compared with OG decreased rumen pool size but did not increase feed intake for cows consuming AL. Digestion responses to forage family were affected by nutrient demand of cows.     

Transition milk stimulates intestinal development of neonatal Holstein calves

Colostrum stimulates gastrointestinal development. Similar to colostrum, transition milk (TM; the first few milkings after colostrum) contains elevated nutrient levels and bioactive components not found in milk replacer (MR), albeit at lower levels than the first colostrum. We hypothesized that feeding neonatal calves TM, compared with MR, for 4 d following colostrum at birth would further stimulate intestinal development. Holstein bull calves were fed 2.8 L of colostrum within 20 min of birth, allocated to 1 of 11 blocks based on birth date and body weight (BW), randomly assigned to MR (n = 12) or TM (n = 11) treatments within block, and fed treatments 3 times per day. Milk from milkings 2, 3, and 4 (TM) of cows milked 2 times daily was pooled by milking number and fed at 1.89 L per feeding; milking 2 was fed at feedings 2 through 5, milking 3 at feedings 6 through 8, and milking 4 at feedings 9 through 12. TM was not pasteurized and contained 17% solids, 5% fat, 7% protein, 4% lactose, and 20 g of IgG per liter on average, whereas MR (as fed) contained 15% solids, 4% protein, 3% fat, 6% carbohydrate, and no IgG. Refusals were similar, so calves fed TM consumed 1.0 Mcal of metabolizable energy per day more than those fed MR. On the morning of d 5, calves were injected i.v. with 5 mg of bromodeoxyuridine per kg of BW and slaughtered 130 min later; then, intestinal sections were excised. Feeding TM, instead of MR, doubled villus length, villus width, villus to crypt ratio, and mucosal length in all intestinal sections, increased submucosal thickness 70% in the proximal and mid jejunum, and tended to increase submucosal thickness in duodenum and ileum. Mucosal surface area was also increased in both the ileum and mid jejunum when feeding TM by 19 and 36%, respectively. Treatment did not alter crypt depth. Bromodeoxyuridine labeling was increased 50% by TM compared with MR in the cells along the epithelium of the crypts and within the villi of all sections, indicating that TM increased cell proliferation compared with MR. Calves fed TM gained more BW than calves fed MR and had improved cough, fecal, nose, and ear scores. We conclude that feeding TM for 4 d following an initial feeding of colostrum stimulates villus, mucosal, and submucosal development in all sections of the small intestine in the first few days of life and improves health and growth.     

黑米矢车菊素-3-O-葡萄糖苷及其月桂酸酰化物对小鼠肠道免疫功能的影响

目的 本文研究了黑米矢车菊素-3-O-葡萄糖苷（Cyanidin-3-O-glucoside, C3G）及其与月桂酸的酰化产物（cyanidin-3-glucoside lauryl ester, L-C3G）对小鼠肠道免疫功能的影响。方法 首先,以小鼠为试验动物,经过低、中及高剂量的C3G和L-C3G灌胃28 d后,测定小鼠的体重、肠道消化酶活性（蛋白酶、淀粉酶、脂肪酶）、肠道pH、肠道组织形态及免疫细胞数量等指标,对C3G和L-C3G的肠道免疫作用进行评价。结果 与空白对照组相比,C3G和L-C3G能够降低小鼠的体重和小鼠肠道pH;提高淀粉酶和蛋白酶活性,降低脂肪酶活性;提高小鼠肠腔绒毛高度,降低隐窝深度,提高消化能力;提高肠道免疫细胞（T细胞、肥大细胞、杯状细胞）的数量。此外,与C3G相比,L-C3G有更强的免疫促进作用。结论 C3G和L-C3G有较好的肠道免疫促进作用。     

Reproductive performance of dairy cows is influenced by prepartum feed restriction and dietary fatty acid source

The objective of this study was to determine the effects of feed restriction and source of dietary fatty acids during the close-up dry period on postcalving reproductive performance of dairy cattle. Thirty-four days before expected calving, pregnant Holstein cows (n = 72; parity 1 to 5) were randomly assigned to 1 of 6 treatments. Treatments were ad libitum (AL) or 24% feed restriction (FR) in combination with 1 of 3 oilseed supplements at 8% of diet dry matter: canola, linola, or flax to enrich the rations with oleic, linoleic, or linolenic fatty acids, respectively. After calving, cows were fed a common lactation diet that contained no oilseeds. Measurements of uterus, corpus luteum, and follicles were obtained by ultrasonography twice weekly from 7 ± 1 d after calving until the first ovulation. Cows (n = 66) were subjected to timed artificial insemination (TAI), and pregnancy was determined 32 d later. Feed-restricted cows had lower dry matter intake and lost more body weight prepartum. Energy balance (Mcal/d) was negative in FR cows prepartum but they had a less severe negative energy balance postpartum. The dietary source of fatty acid did not affect energy balance. Cows fed AL had a higher incidence of uterine infections (10/37 vs. 2/35) but tended to have fewer ovarian cysts (2/37 vs. 7/35) than FR cows. Mean (±SE) interval from calving to uterine involution did not differ among dietary treatments (26.8 ± 1.8 d). Interval from calving to first ovulation was longer in cows fed canola than in those fed either linola or flax (34.7 ± 3.1 vs. 23.7 ± 3.2 and 21.0 ± 3.1 d, respectively). A greater percentage of cows fed AL conceived to the first TAI (47.1 vs. 18.8) and tended to have fewer mean days open (157 ± 10.8 vs. 191 ± 10.1) than cows fed FR. In summary, FR cows had a lower incidence of uterine infections, but they were less fertile as reflected by a lower percent pregnancy to first TAI and increased days open. Cows fed diets enriched in linoleic or linolenic fatty acids had a lesser incidence of ovarian cysts and ovulated sooner with no effect on energy balance or fertility.     

Nutrient demand interacts with forage family to affect intake and digestion responses in dairy cows

The effect of feed intake in the preliminary period on responses to diets containing alfalfa silage or orchardgrass silage was evaluated using 8 ruminally and duodenally cannulated Holstein cows in a crossover design experiment with a 14-d preliminary period and two 15-d treatment periods. Responses measured were DMI, rates of fiber digestion and passage, and milk production. Cows were 139 ± 83 (mean ± SD) d in milk at the beginning of the preliminary period. During the preliminary period, 3.5% fat-corrected milk yield ranged from 23.9 to 47.6 kg/d (mean = 36.9 kg/d) and preliminary voluntary DMI (pVDMI) ranged from 14.2 to 21.3 kg/d (mean = 18.6 kg/d). The 2 treatments were a diet containing alfalfa silage as the sole forage (AL) and a diet containing orchardgrass silage as the sole forage (OG). Alfalfa silage contained 43% neutral detergent fiber (NDF; dry-matter basis) and orchardgrass silage contained 48% NDF; diets contained ∼23% forage NDF and 27% total NDF, so forage-to-concentrate ratio was 53:47 for AL and 48:52 for OG. Digestibility of NDF was lower for AL in the rumen and whole tract compared with OG, and milk fat concentration tended to be greater for OG than for AL. Mean 3.5% fat-corrected milk yield and DMI were not different between AL and OG. Response of DMI to forage family depended on pVDMI, as indicated by a significant interaction between treatment and pVDMI in predicting DMI. As pVDMI increased, DMI increased when cows were fed AL but not when they were fed OG. That is, as appetite increased, intake was more restricted for the more physically filling OG than for the less physically filling AL. This more positive DMI response to AL over OG among high-pVDMI cows is corroborated by interactions between treatments and pVDMI for both ruminal NDF turnover rate and indigestible NDF passage rate response. Therefore, the effects of alfalfa and orchardgrass forages on intake and fiber digestion depended on the extent to which fill limited feed intake of an individual cow.     

Effects of dietary zinc source on the metabolic and immunological response to lipopolysaccharide in lactating Holstein dairy cows

The objectives of this study were to evaluate the effects of replacing 40 mg/kg of Zn from Zn sulfate (control; CON) with Zn AA complex (AvZn) on metabolism and immunological responses following an intravenous lipopolysaccharide (LPS) challenge in lactating cows. Cows were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF AvZn (PF-AvZn; 5 mL of saline; n = 5), (3) LPS euglycemic clamp control (LPS-CON; 0.375 μg of LPS/kg of BW; n = 5), and (4) LPS euglycemic clamp AvZn (LPS-AvZn; 0.375 μg of LPS/kg of BW; n = 5). Cows were enrolled in 3 experimental periods (P). During period 1 (3 d), cows received their respective dietary treatments and baseline data were obtained. During period 2 (P2; 2 d), a 12-h LPS euglycemic clamp was conducted or cows were PF to their respective dietary counterparts. During period 3 (P3; 3 d), cows received their dietary treatment and consumed feed ad libitum. Mild hyperthermia (1°C) was observed in LPS cows at 3 h postbolus. Throughout P2, the rectal temperature of LPS-AvZn cows was decreased (0.3°C) relative to LPS-CON cows. Administrating LPS decreased dry matter intake (47%) during P2, and by experimental design the pattern was similar in PF cohorts. During P3, dry matter intake from LPS cows remained decreased (15%) relative to PF cows. Milk yield from LPS cows decreased (54%) during P2 relative to PF cows, but it was similar during P3. During P2, somatic cell count increased 3-fold in LPS cows relative to PF controls. Dietary AvZn tended to decrease somatic cell count (70%) during P3 relative to LPS-CON cows. Insulin increased 7-fold in LPS cows at 12 h postbolus and remained increased (4-fold) for the duration of P2. Circulating glucagon from LPS cows increased (65%) during P2, and supplementing AvZn blunted the increase (30% relative to LPS-CON). During P2, circulating cortisol increased 7-fold post-LPS infusion relative to PF cows, and supplementing AvZn decreased cortisol (58%) from 6 to 48 h postbolus relative to LPS-CON cows. Administrating LPS increased circulating LPS-binding protein and serum amyloid A (3- and 9-fold, respectively) relative to PF cows. Compared with LPS-CON, LPS-AvZn cows had increased circulating serum amyloid A (38%) 24 h postbolus. The 12-h total glucose deficit was 36 and 1,606 g for the PF and LPS treatments, respectively, but was not influenced by Zn source. In summary, replacing a portion of the Zn sulfate with Zn AA complex appeared to reduce the inflammatory response but had no effect on the glucose deficit.     

Reducing gut effects from Cryptosporidium parvum infection in dairy calves through prophylactic glucagon-like peptide 2 therapy or feeding of an artificial sweetener

Glucagon-like peptide 2 (GLP-2) therapy was shown previously to reduce inflammation-related gut damage from coccidiosis in dairy calves, and feeding of artificial sweetener stimulates GLP-2 secretion from intestinal L cells. The purpose of this study was to determine whether GLP-2 treatment or artificial sweetener feeding beginning 1 wk before an experimental inoculation with the coccidian parasite Cryptosporidium parvum can reduce infection-related intestinal damage in Holstein bull calves. Newborn calves were assigned to 1 of 4 treatment groups of 6 calves each, including noninfected control calves injected s.c. every 12 h with control buffer (CON), infected control calves injected s.c. every 12 h with control buffer (INF), infected calves injected s.c. every 12 h with 50 µg/kg of body weight of GLP-2 (GLP2), and infected calves injected s.c. every 12 h with control buffer and supplemented in the diet with Sucram (Pancosma, Geneva, Switzerland) at 400 mg/kg of dry matter of milk replacer (SUC). Treatments were initiated on d 1, and calves in INF, GLP2, and SUC were orally dosed on d 8 with 12,500 C. parvum oocysts. Fecal scores were recorded daily, plasma was collected on d 1, 8, 12, 15, and 18 to evaluate markers of inflammation, and fecal samples were collected on d 1, 8, and every other day thereafter to determine the presence of oocysts. Calves were euthanized on d 18 for collection of intestinal tissues and histological and gene expression analyses. Relative to CON, calves in INF exhibited an increase in diarrhea severity, increased plasma serum amyloid A concentration on d 15 and 18, reduced intestinal villus height, increased villus apoptosis and crypt cell proliferation, and increased intestinal mRNA expression of MARVELD2 and GPX2. However, calves in SUC and GLP2 had reduced diarrhea severity and fecal C. parvum oocyst shedding, reduced plasma serum amyloid A concentration on d 15 and 18, and, depending on the intestinal segment, increased villus height, reduced crypt cell proliferation, and reduced mRNA expression of MARVELD2, GPX2, and other tight junction proteins relative to INF. Lastly, GLP2 and SUC exhibited increased intestinal mass-to-length ratio and decreased length-to-empty body weight ratio relative to INF. Our findings suggest that GLP-2 and Sucram treatments administered before a low-level C. parvum exposure may contribute to fewer effects on intestinal integrity, morphology, and inflammation in response to infection, and shorter, denser intestines.     

山楂、麦芽及膳食纤维对维生素缺乏幼鼠肠道功能的影响

维生素类微量营养成分缺乏在儿童中普遍存在,针对此问题,本研究以断奶鼠为模型动物,评估在VB1、VB2、VB6和VA缺乏状态下,山楂和麦芽及其与膳食纤维复合对肠道功能的改善作用。结果显示,高剂量山楂和麦芽组、高剂量复合组都能够显著促进模型组小鼠的肠运动性。与正常对照组相比,维生素缺乏导致大鼠的体质量增量、摄食量和饲料利用率分别显著降低了34.29%、17.78%和19.24%（P＜0.05）,空肠和回肠的绒毛高度和隐窝深度比值分别显著降低了37.30%和36.79%（P＜0.05）,粪便中乙酸和总短链脂肪酸（short chain fatty acid,SCFA）含量分别显著降低了37.63%和43.87%（P＜0.05）。与维生素缺乏模型组相比,高剂量山楂和麦芽组显著改善了维生素缺乏大鼠的摄食量和体质量增量,其中摄食量和体质量增量分别增加了7.84%和14.77%（P＜0.05）,低剂量复合组的食物利用率显著提高11.58%。与维生素缺乏模型组相比,高剂量山楂和麦芽组和低剂量复合组的空肠绒毛高度和隐窝深度的比值分别显著增加了52.65%和47.35%（P＜0.05）;高剂量山楂和麦芽组粪便中乙酸和总SCFA含量分别显著提高了46.86%和78.00%（P＜0.05）,低剂量复合组粪便中乙酸和总SCFA含量分别显著提高了43.74%和44.91%（P＜0.05）。高剂量复合物组会使得肠道菌群中副拟杆菌过度生长,降低菌群多样性,引起菌群失调。高剂量山楂和麦芽组可调控维生素缺乏大鼠肠道菌群结构,增加乳杆菌属和阿克曼氏菌属的丰度。综上表明,高剂量山楂和麦芽组对大鼠肠道菌群具有一定的改善作用,低剂量复合组与高剂量山楂和麦芽组对肠道菌群的影响相似度较高,都能促进产SCFA特定菌属的生长,提高肠道SCFA含量,改善肠道组织形态,从而改善维生素缺乏大鼠肠道吸收功能,促进机体生长发育,实验结果可为功能食品的开发提供科学依据。     

绿原酸缓解镉暴露致大鼠肠道损伤

目的：探讨绿原酸缓解镉暴露致大鼠肠道损伤。方法：将32 只大鼠随机分为空白对照组（control, CON）、镉损伤模型组（CdCl2,Cd）、镉损伤模型＋绿原酸治疗组（CdCl2＋chlorogenic acid,Cd＋CGA）、 镉损伤模型＋葵花仁提取物治疗组（CdCl2＋sunflower seed extract,Cd＋SSE）。每日灌胃氯化镉6 mg/kg、绿原 酸50 mg/kg、葵花仁提取物中按绿原酸的量计50 mg/kg,对照组给予相同体积的蒸馏水,连续14 d,定期称量体 质量和采食量。处死后取血液、肝脏、肾脏和肠道。观察肠道黏膜形态,统计黏膜损伤评分,计算绒毛高度, 隐窝深度并测定谷草转氨酶（aspartate aminotransferase,AST）、谷丙转氨酶（alanine aminotransferase,ALT） 活力和血清白蛋白（serum albumin,ALB）水平。结果：绿原酸和葵花仁提取物显著增加镉损伤大鼠体质量,绿 原酸显著增加采食量（P＜0.05）;绿原酸和葵花仁提取物显著缓解由于镉损伤造成的肝脏指数和回肠指数的失 常（P＜0.05）,绿原酸显著降低肾脏指数和空肠指数（P＜0.05）;绿原酸和葵花仁提取物显著抑制AST和ALT的 活力（P＜0.05）,同时增加镉损伤大鼠肠道绒毛高度和隐窝深度（P＜0.05）,形态学观察结果显示绿原酸能有效 地抑制镉造成的黏膜细胞死亡。结论：绿原酸可有效缓解镉造成的肠道损伤。     

Effects of late-gestation heat stress independent of reduced feed intake on colostrum,metabolism at calving,and milk yield in early lactation of dairy cows

The objective of this study was to differentiate the effects of acute heat stress (HS) from those of decreased dry matter intake (DMI) during the prepartum period on metabolism, colostrum, and subsequent production of dairy cows. Holstein dairy cows (n = 30) with similar parity and body weight were randomly assigned to 1 of 3 treatments on 45 d before calving: (1) cooled (CL, n = 10) conditions with ad libitum feed intake, (2) HS conditions with ad libitum feed intake (n = 10), and (3) pair-fed cooled (CLPF, n = 10) with reduced DMI similar to the HS group while housed under cooled conditions. The reduction in the amount of feed offered to the CLPF cows was calculated daily as the percentage decrease from the average DMI of HS cows relative to the CL cows. For CLPF and CL cows, barns provided shade, sprinklers, and fans, whereas the HS cows were provided only with shade. Cows in all groups received individually the same total mixed ration. Cows were dried off 60 d before the expected calving. Cows in the HS group and, by design, the CLPF cows had reduced DMI (~20%) during the experiment. Heat stress decreased gestation length, first colostrum yield, and calf birth weight compared with CL and CLPF cows. Milk yield decreased 21% (5 kg) in the HS and 8% (2 kg) in CLPF cows, indicating that reduced feed intake during late gestation accounted for 60% of the total reduced milk yield. The CLPF cows exhibited an elevated NEFA concentration compared with the CL and HS cows. The HS cows had a greater mRNA abundance of HSP70 in the peripheral blood leukocytes at 21 d prepartum compared with the other groups. At calving, the mRNA abundance of HSP70 was greater in HS cows, followed by CLPF, compared with the CL cows. In conclusion, HS during the late gestation period caused metabolism and production differences, which were only partially attributed to reduced feed intake in dairy cows.     

Effect of chromium on bioenergetics and leukocyte dynamics following immunoactivation in lactating Holstein cows

Activated immune cells are insulin sensitive and utilize copious amounts of glucose. Because chromium (Cr) increases insulin sensitivity and may be immunomodulatory, our objective was to evaluate the effect of supplemental Cr (KemTrace Cr propionate, 20 g/d; Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and immune system dynamics following an intravenous endotoxin challenge in lactating Holstein cows. Twenty cows (320 ± 18 d in milk) were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF and Cr supplemented (PF-Cr; 5 mL of saline; n = 5), (3) lipopolysaccharide (LPS)-euglycemic clamp and control supplemented (LPS-CON; 0.375 µg/kg of body weight LPS; n = 5), and (4) LPS-euglycemic clamp and Cr supplemented (LPS-Cr; 0.375 µg/kg of body weight LPS; n = 5). The experiment was conducted serially in 3 periods (P). During P1 (3 d), cows received their respective dietary treatments and baseline values were obtained. At the initiation of P2 (2 d), either a 12-h LPS-euglycemic clamp was conducted or cows were PF to their respective dietary counterparts. During P3 (3 d), cows consumed feed ad libitum and continued to receive their respective dietary treatment. During P2, LPS administration decreased dry matter intake (DMI; 40%) similarly among diets, and by experimental design the pattern and magnitude of reduced DMI were similar in the PF cohorts. During P3, LPS-Cr cows tended to have decreased DMI (6%) relative to LPS-CON cows. Relative to controls, milk yield from LPS-challenged cows decreased (58%) during P2 and LPS-Cr cows produced less (16%) milk than LPS-CON cows. During P3, milk yield progressively increased similarly in LPS-administered cows, but overall milk yield remained decreased (24%) compared with PF controls. There were no dietary treatment differences in milk yield during P3. Circulating insulin increased 9- and 15-fold in LPS-administered cows at 6 and 12 h postbolus, respectively, compared with PF controls. Compared with LPS-CON cows, circulating insulin in LPS-Cr cows was decreased (48%) at 6 h postbolus. Relative to PF cows, circulating LPS binding protein and serum amyloid A from LPS-administered cows increased 2- and 5-fold, respectively. Compared with PF cows, blood neutrophil counts in LPS-infused cows initially decreased, then gradually increased 163%. Between 18 and 48 h postbolus, the number of neutrophils was increased (12%) in LPS-Cr versus LPS-CON cows. The 12-h total glucose deficit was 220 and 1,777 g for the PF and LPS treatments, respectively, but glucose utilization following immune activation was not influenced by Cr. In summary, supplemental Cr reduced the insulin response and increased circulating neutrophils following an LPS challenge but did not appear to alter the immune system's glucose requirement following acute and intense activation.