Effects of colostrum intake and of ingested proliferation of small intestinal crypt cells was not Metabolic changes

J .W. Blum, H. Hammon Livestock Production Science 66 2000 151 –159 153 ¨ et al., 1997; Le Huerou-Luron et al., 1998; Blum and cal amounts of hIGF-I 3.8 mg l, secreted with milk Hammon, 1999a,b. in amounts up to 0.2 g l by transgenic rabbits had been added, villus height, villus circumference and crypt depth were not significantly modified and the

2. Effects of colostrum intake and of ingested proliferation of small intestinal crypt cells was not

¨ hormones and growth factors on the GIT enhanced Fah, Hammon, Brem and Blum, unpub- lished observations. Thus, effects of IGF-I on Ingestion of colostrum has marked effects on GIT postnatal GIT development are controversial, in development and function, and affects digestive accordance with studies in pigs and laboratory enzymes and GI hormones Guilloteau et al., 1997; animals Burrin et al., 1996, 1999; Burrin, 1997. ¨ ¨ Hadorn et al., 1997; Buhler et al., 1998; Le Huerou- Luron et al., 1998, and absorptive capacity Ham- mon and Blum, 1997a. Colostrum intake modifies

3. Metabolic changes

GIT development and digestive and absorptive ca- pacities in neonates, not only through provision of Intake of colostrum causes considerable metabolic nutrients, minerals, vitamins and energy, but proba- changes. In new-born calves, as expected, blood bly also due to effects of growth-promoting factors plasma concentrations of total protein rise as a in various species, including calves Kelly, 1994; consequence of absorbed immunoglobulins especial- Burrin et al., 1995, 1996; Odle et al., 1996; Xu, ly IgG. Changes depend on the timing and amounts ¨ 1996; Blattler, Hammon and Blum, unpublished of ingested colostrum and IgG, but are not altered observations. after intake of milk or milk replacer Hadorn and ¨ There is recent evidence that amniotic IGF-I Blum, 1997; Hammon and Blum, 1999; Kuhne et al., ingested by foetal sheep enhances GIT development 2000; Rauprich et al., 2000a,b; Zanker et al., 2000. Kimble et al., 1999. IGF-I and insulin receptor Plasma albumin concentrations partially reflect mRNAs are present in the small intestine of 8-day- hepatic synthesis and mostly increase during the first old calves Cordano, Hammon and Blum, unpub- week of life, dependent on the colostrum supply ¨ lished observations. Furthermore, IGF-I, IGF-II, Hadorn et al., 1997; Kuhne et al., 2000; Rauprich et 3 Long-R -IGF-I an IGF-I analogue, which binds only al., 2000a. slightly to plasma IGF binding proteins and insulin Total and individual plasma free EAA increased bind to specific receptors in the duodenum, jejunum, on day 1 of life after intake of colostrum, but not ileum and colon of neonatal calves Baumrucker et milk replacer, and remained higher if calves were fed al., 1994b; Hammon and Blum, 1998c. Binding colostrum for 3 days than if colostrum was provided capacities of IGF-I, IGF-II and insulin in the mucosa only at the first meal Hammon and Blum, 1999. of the small intestine and colon were greater in Interestingly, plasma free glutamate concentrations 8-day-old calves fed colostrum for 3 days than in increased, whereas those of free glutamine de- those fed milk replacer Hammon and Blum, 1998c, creased, in colostrum-fed calves only, possibly re- and IGF-I binding capacity in the small intestinal flecting enhanced tissue glutamine uptake for exam- mucosa was upregulated by orally-administered IGF- ple by rapidly dividing cells, such as those of the I Baumrucker et al., 1994b. Furthermore, orally GIT due to colostrum feeding Hammon and Blum, administered recombinant human IGF-I rhIGF-I, 1999. Furthermore, we found that plasma EAA which has the same structure as bovine IGF-I, concentrations were transiently decreased if the stimulated growth of the small intestine in neonatal intake of the first colostrum was delayed by 24 h 3 calves based on [ H]-thymidine incorporation into Zanker et al., 2000. enterocytes ex vivo Baumrucker et al., 1994b. Plasma urea concentrations, if there are no hepatic These data are in accordance with studies in other and kidney dysfunctions, are dependent on intake, species, such as pigs Burrin et al., 1996; Odle et al., synthesis and degradation of protein, as we have 1996; Xu, 1996. However, in calves fed a formula shown in neonatal calves Hadorn et al., 1997; ¨ for the first 8 days of life, to which supraphysiologi- Kuhne et al., 2000; Zanker et al., 2000. In calves 154 J .W. Blum, H. Hammon Livestock Production Science 66 2000 151 –159 fed a milk-based formula with similar amounts of activities in plasma decrease rapidly, they are likely nutrients as colostrum but only traces of growth mostly degraded. factors especially IGF-I, urea concentrations were Amount and timing of colostrum intake affect elevated Rauprich et al., 2000b. This suggests that plasma glucose in neonatal calves. Thus, plasma non-nutritional factors such as IGF-I and insulin in glucose increased less after intake of the first colos- colostrum exert an anabolic effect and thereby trum than of milk replacer if milk replacer contained ¨ reduce plasma urea concentrations. more lactose than colostrum Grutter and Blum, Nitrate NO is ingested through feed and water 1991a; Hadorn et al., 1997; Hammon and Blum, 3 ¨ or is endogenously produced from nitric oxide NO 1998b; Kuhne et al., 2000. However, postprandial and nitrite NO . The substrate for the formation of plasma glucose concentrations on the following days 2 NO is arginine Arg, which under the influence of increased more in calves initially fed colostrum than NO synthases NOS is transformed into citrulline. milk replacer, glucose or water, indicating prolonged Interactions between NO and urea production, and effects of early colostrum intake on glucose metabo- thus with nitrogen metabolism, have been demon- lism. Colostrum intake also positively influenced strated in cattle Kahl et al., 1997. Most interesting- absorptive capacity of carbohydrates, such as xylose ly and not reported before, we found very high NO Hammon and Blum, 1997a; Rauprich et al., 2000b. x 5 NO 1 NO , primarily NO concentrations in The plasma lipid and fat-soluble vitamin status in 2 3 3 blood plasma, saliva and urine in new-born calves the neonatal period is influenced by the amount and before the first meal, while concentrations in their timing of ingested colostrum. Thus, if colostrum was cerebrospinal fluid and in the blood plasma and milk withheld for the first 24 h after birth, plasma non- of their dams were very low Blum et al., 1998. esterifed FA NEFA increased, whereas plasma Plasma concentrations decreased within the first days concentrations of triglycerides TG, phospholipids of life, but still remained relatively high for several PL, cholesterol, and essential and non-essential FA months. The data indicate significant endogenous in TG, PL and cholesterol ester fractions, and of NO production in neonatal calves. Different feeding fat-soluble pro- vitamins carotene, retinol, a- 3 feeding colostrum or milk replacer in different tocopherol remained lower than in calves fed colos- amounts or delayed for 24 after birth and adminis- trum immediately after birth Blum et al., 1997; 3 tration of GH and Long-R -IGF-I had no effects on Hadorn et al., 1997; Zanker, 1997. Besides de- NO and NO concentrations in blood plasma, saliva creased intake, the mechanisms of absorption of FA 3 2 and urine of neonatal calves, except when . 200 and fat-soluble vitamins in calves not fed colostrum m mol NO or NO were fed per kg body weight. on the first day of life may be responsible for the 2 3 Thus, we concluded that the high NO concen- subsequent impaired FA and fat-soluble vitamin 3 trations in blood plasma and the high amounts status. In addition, impaired post-absorptive transport excreted in saliva and urine in neonatal calves are and distribution of these substances for example, primarily of a constitutional nature. due to failure of the induction and production of Activities of g-glutamyltransferase g-GT, lactate transport proteins is also possible if colostrum is not dehydrogenase LDH, glutamate dehydrogenase provided shortly after birth. In contrast to fat-soluble GLDH and aspartate aminotransferase AST were vitamins, plasma water-soluble vitamins B-6, B-12 very high in first milked colostrum and then de- and folic acid were not dependent on timing of creased to low values in mature milk Zanker, 1997. colostrum feeding Blum et al., 1997. We have Activities of these enzymes in neonatal calf plasma repeatedly shown that plasma TG, PL and choles- transiently increased after intake of first colostrum, terol concentrations are higher in calves fed colos- but not of milk replacer, indicating that these en- trum for 3 days than in those fed only milk replacer ¨ zymes were absorbed from colostrum Baumrucker Hammon and Blum, 1998b; Kuhne et al., 2000. et al., 1994a; Hadorn and Blum, 1997; Zanker, 1997; Interestingly, plasma concentrations of TG, PL, Egli and Blum, 1998; Hammon and Blum, 1998b. cholesterol, and essential and non-essential FA were The biological importance of increased plasma en- still lower in calves fed milk replacer than in calves zyme activities, if any, is not known. Because their fed the same amount of these metabolites but via J .W. Blum, H. Hammon Livestock Production Science 66 2000 151 –159 155 colostrum Rauprich et al., 2000b. The lipid status markedly than did all other studied hormones if food seems therefore not only to be dependent on the was withheld for 24 h in 8-day-old calves Kin- ingested amount of fat, but seems to be enhanced by sbergen et al., 1994; Hadorn et al., 1997. colostrum intake. In addition, TG concentrations Pancreatic glucagon has antagonistic effects to increased more in calves fed a milk replacer sup- insulin. In our studies, plasma concentrations after ¨ plemented with hIGF-I Fah, Hammon, Brem and first feeding increased more in calves which received Blum, unpublished observations. Mechanisms for colostrum than in those fed milk replacer Hammon these colostrum effects are not known. We speculate and Blum, 1998b. Additional colostrum feedings that bioactive components such as IGF-I and in- during the first 2 days of life increased glucagon sulin modify digestion and absorption of FA, by concentrations but, after day 3 of life, glucagon possibly altering lipase activity or FA binding pro- concentrations were higher in milk replacer-fed than ¨ teins. colostrum-fed calves Kuhne et al., 2000; Rauprich We have not found significant effects of the et al., 2000b. amounts of colostrum fed or the timing of the first Plasma cortisol concentrations decrease during the colostrum feeding on calcium, magnesium, inorganic first week of life in neonatal calves and transiently phosphorus and iron concentrations Zanker, 1997. decrease after intake of colostrum, milk or milk replacer Ronge and Blum, 1988; Baumrucker and Blum, 1994; Lee et al., 1995; Hadorn et al., 1997.

4. Endocrine changes Plasma cortisol concentrations during the first week