Laboratory of Colostrum Research

Digestive

Feeding Colostrum, Its Composition and Feeding Duration Variably Modify Proliferation and Morphology of the Intestine and Digestive Enzyme Activities of Neonatal Calves1 ,2

Urs Blattler*,3, Harald M. Hammon*, Claudine Morel*, Chantal Philipona*, Andrea Rauprich*, Véronique Romé , Isabelle Le Hu?rou-Luron , Paul Guilloteau and Jürg W. Blum*4

* Division of Nutritional Pathology, Faculty of Veterinary Medicine, CH-3012 Berne, Switzerland and Unité Mixte de Recherches sur le Veau et le Porc, Institut National de la Recherches Agronomique, F-35042 Rennes, France

4To whom correspondence should be addressed at Division of Nutritional Pathology, Faculty of Veterinary Medicine, University of Berne, Bremgartenstr. 109a, CH-3012 Berne, Switzerland. E-mail: blum@itz.unibe.ch

We studied the effects of amounts of colostrum consumed on intestinal morphology and proliferation and digestive enzyme activities in neonatal calves. Group GrCmax calves were fed colostrum from the first milking undiluted on d 1-3 and diluted with 25, 50, 75 and 75 parts of a milk replacer on d 4-7. Group GrC1-3 calves were fed colostrum from milkings 1-6 up to d 3 and then a milk replacer up to d 7. Group GrF1-3 calves were fed a milk-based formula (containing only traces of growth factors and hormones) up to d 3 and then a milk replacer up to d 7. Calves were killed on d 8. Differences in feeding affected villus sizes and villus height/crypt depth ratios in the duodenum (GrCmax > GrC1-3), villus areas and villus height/crypt depth ratios in the jejunum (GrC1-3 > GrF1-3) and crypt depths in the colon (GrF1-3 > GrC1-3). Furthermore, different feeding protocols affected the proliferation rates of epithelial cells in the duodenum (GrC1-3 > GrCmax; GrC1-3 > GrF1-3) and the jejunum (GrF1-3 > GrC1-3; based on Ki-67 labeling). Lipase activities in the pancreas were influenced by colostrum feeding (GrCmax > GrC1-3). Colostrum intake differentially affected intestinal epithelial surface and proliferation and enzyme activities. Feeding high amounts of first colostrum seemed to enhance the survival of mature mucosal epithelial cells in selected parts of the small intestine, whereas the lack of colostrum seemed to decrease epithelial growth.

Key Words: neonates - colostrum - intestine - pancreas - calves

Nonnutritive Factors in Colostrum Enhance Myofibrillar Protein Synthesis in the Newborn Pig

MARTA L. FIOROTTO, TERESA A. DAVIS, PETER J. REEDS and DOUGLAS G. BURRIN

USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, U.S.A.

Correspondence and reprint requests: Marta L. Fiorotto, Ph.D., CNRC, Department of Pediatrics, 1100 Bates St., Houston, TX 77030, U.S.A.

Colostrum is a complex source of nutrients, immune factors, and bioactive substances consumed by newborn mammals. In previous work, we observed that protein synthesis in the skeletal muscle of newborn piglets is enhanced when they are fed colostrum rather than a nutrient-matched formula devoid of growth factors. To elucidate the mechanisms responsible for this response, we contrasted the fractional rates of sarcoplasmic and myofibrillar protein synthesis of newborn piglets that received only water with those fed for 24 h with colostrum, a nutrient-matched formula, or mature sow’s milk. Compared with water, feeding resulted in a 2.5- to 3-fold increase in total skeletal muscle protein synthesis, and this increase was 28% greater in the colostrum-fed than either the formula- or mature milk-fed piglets. Feeding also stimulated muscle ribosome and total polyadenylated RNA accretion. Ribosomal translational efficiency, however, was similar across all fed groups. The greater stimulation of protein synthesis in colostrum-fed pigs was restricted entirely to the myofibrillar protein compartment and was associated with higher ribosome and myosin heavy chain mRNA abundance. Taken together, these data suggest that nonnutritive factors in colostrum enhance ribosomal accretion and muscle-specific gene transcription that, in turn, stimulate specifically the synthesis of myofibrillar proteins in the skeletal musculature of the newborn.

Abbreviations:
FSR, fractional synthesis rate
MHC, myosin heavy chain
GAPDH, glyceraldehyde phosphate dehydrogenase
polyA, polyadenylated RNA
rRNA, ribosomal RNA

The Protective Effects of Lactoferrin Feeding against Endotoxin Lethal Shock in Germfree Piglets

Wang J. Lee,1, Jeffrey L. Farmer,2 Milo Hilty,3 and Yoon B. Kim1,*

Finch University of Health Sciences/The Chicago Medical School, North Chicago,1 and Abbott Laboratories, Abbott Park,2 Illinois 60064, and Ross Laboratories, Columbus, Ohio 432153

Received 10 November 1997/Returned for modification 22 December 1997/Accepted 15 January 1998

The unique germfree, colostrum-deprived, immunologically "virgin" piglet model was used to evaluate the ability of lactoferrin (LF) to protect against lethal shock induced by intravenously administered endotoxin. Piglets were fed LF or bovine serum albumin (BSA) prior to challenge with intravenous Escherichia coli lipopolysaccharide (LPS), and temperature, clinical symptoms, and mortality were tracked for 48 h following LPS administration. Prefeeding with LF resulted in a significant decrease in piglet mortality compared to feeding with BSA (16.7 versus 73.7% mortality, P < 0.001). Protection against the LPS challenge by LF was also correlated with both resistance to induction of hypothermia by endotoxin and an overall increase in wellness, as quantified by a toxicity score developed for these studies. In vitro studies using a flow cytometric assay system demonstrated that LPS binding to porcine monocytes was inhibited by LF in a dose-dependent fashion, suggesting that the mechanism of LF action in vivo may be inhibition of LPS binding to monocytes/macrophages and, in turn, prevention of induction of monocyte/macrophage-derived inflammatory-toxic cytokines.

Infect. Immun., 12 1995, 4917-4920, Vol 63, No. 12

Inhibition of S-fimbria-mediated adhesion to human ileostomy glycoproteins by a protein isolated from bovine colostrum

AC Ouwehand, PL Conway and SJ Salminen

Department of General and Marine Microbiology, Goteborg University, Sweden.

The aim of this study was to isolate and purify the component in bovine colostrum which is responsible for the inhibition of S-fimbria-mediated adhesion of Escherichia coli. Whey from defatted colostrum was fractionated by ultrafiltration, and the < 100K, < 30K, and < 10K fractions and the colostral whey were tested for inhibition of in vitro adhesion of radiolabelled S-fimbria-bearing E. coli to human ileostomy glycoproteins, which provide a model for human intestinal mucus. The inhibiting compound was purified from a dialyzed < 30K fraction with an anion exchange column which was eluted with a NaCl gradient (0 to 1.0 M). The compound was found to be a heat-resistant but pepsin-sensitive protein with an Mr of approximately 18,000 and an isoelectric point of approximately 5.75. The protein appears to block receptor sites for S- fimbriae on ileostomy glycoproteins, with steric hindrance being the most likely mechanism. Analysis of the amino acid sequence of the amino terminus of the 18K protein showed similarity with the sequence of beta- lactoglobulin.

Arch. Dis. Child. 1994 70: c356-c357.

Bovine colostrum immunoglobulin concentrate for cryptosporidiosis in AIDS

P Heaton

Archives of Disease in Childhood, Vol 69, 451-453, Copyright ? 1993 by Archives of Disease in Childhood.

Bovine colostrum immunoglobulin concentrate for cryptosporidiosis in AIDS

J Shield, C Melville, V Novelli, G Anderson, I Scheimberg, D Gibb and P Milla

Department of Infectious Diseases, Hospital for Sick Children, London.

Lactobin-R is a commercial hyperimmune bovine colostrum with potent anticryptosporidial activity. It was administered to a 4 year old child with AIDS and severe diarrhoea associated with cryptosporidiosis. There was significant clinical improvement in the diarrhoea and permanent elimination of the parasite from the gut as assessed through serial jejunal biopsy and stool specimens.

Infect. Immun., Dec 1992, 5132-5138, Vol 60, No. 12

Characterization of a > 900,000-M(r) Cryptosporidium parvum sporozoite glycoprotein recognized by protective hyperimmune bovine colostral immunoglobulin

C Petersen, J Gut, PS Doyle, JH Crabb, RG Nelson and JH Leech

Parasitology Laboratory, San Francisco General Hospital, California.

Cryptosporidium parvum, a zoonotic Apicomplexan pathogen, causes profound diarrhea, malnutrition, and dehydration in patients with AIDS. A less severe, self-limited disease occurs in immunocompetent individuals, particularly children, animal handlers, and residents of the developing world. Very little is known about the biology of the organism, the pathophysiology of the disease process, or the mechanism of protective immunity. There is no effective therapy for cryptosporidiosis, but hyperimmune bovine colostrum raised against Cryptosporidium oocysts and sporozoites has ameliorated infection and disease in some patients with AIDS, and a variety of monoclonal antibodies, as well as hyperimmune bovine colostrum, have significantly reduced cryptosporidial infection of mice and calves. We report here the identification and initial characterization of a > 900,000-M(r) Cryptosporodium sporozoite glycoprotein (GP900) that is a prominent antigen recognized by protective hyperimmune bovine colostral immunoglobulin. Three of six murine anticryptosporidial monoclonal antibodies reacted with GP900, indicating that the molecule is highly immunogenic in mice as well as in cows. GP900 is Triton X-100 soluble and N glycosylated. Western blotting of the N-deglycosylated protein, detected with antibodies eluted from recombinant clones expressing a partial GP900 fusion protein, suggested that the polypeptide backbone of the glycoprotein has an M(r) of < 190,000. GP900 is encoded by a single-copy gene that resides on the largest Cryptosporidium chromosome.

American Journal of Clinical Nutrition, Vol 54, 829-835, Copyright ? 1991 by The American Society for Clinical Nutrition, Inc

ORIGINAL RESEARCH COMMUNICATIONS

Essential fatty acid composition of human colostrum triglycerides: its relationship with adipose tissue composition

JC Martin, T Niyongabo, L Moreau, JM Antoine, M Lanson, C Berger, F Lamisse, P Bougnoux and C Couet

Laboratoire de Biologie des Tumeurs, Hopital Bretonneau, Tours, France, Paris.

The relationships between essential fatty acid (EFA) composition of colostrum and white adipose tissue (WAT) were examined on day 5 after delivery in 69 healthy women. Fatty acid composition was assessed by capillary gas chromatography, and 33 fatty acids were detected in colostrum and in WAT. Total polyunsaturated fatty acid (PUFA) content was similar in colostrum and in WAT (15.7 +/- 3.1% and 16.1 +/- 3.8%, respectively), but long-chain PUFA content was higher in colostrum than in WAT (2.9 +/- 0.6% and 1 +/- 0.2%, respectively; P less than 0.001). The concentrations of linoleic acid were significantly correlated between colostrum and WAT (r = 0.77, P less than 0.0001). No correlation was found for alpha-linolenic acid. The relationships between long-chain PUFA composition of colostrum and WAT suggested that individual factors along with tissue specificity of the mammary gland are involved in either the capacity of desaturating and chain- elongating pathways and/or incorporation of long-chain PUFAs into colostrum.

Gastroenterology, Vol 98, 486-489, Copyright ? 1990 by American Gastroenterological Association

Cessation of Cryptosporidium-associated diarrhea in an acquired immunodeficiency syndrome patient after treatment with hyperimmune bovine colostrum

BL Ungar, DJ Ward, R Fayer and CA Quinn

Division of Tropical Public Health, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Cryptosporidium is a parasite of the human gastrointestinal tract that can cause life-threatening diarrhea in immunodeficient patients. Although more than 80 agents have been tried with occasional anecdotal success, treatment remains primarily limited to hydration. A 38-yr-old homosexual man with antibody to human immunodeficiency virus and Cryptosporidium-related diarrhea is described. The patient excreted 6- 12 L of stool per day for at least 3 mo, 2 of them spent in the hospital. Trials with more than 6 antidiarrheal medications were ineffective. The patient received bovine colostrum hyperimmune to Cryptosporidium by direct duodenal infusion. During infusion, the patient's fecal output decreased to less than 2 L per day, and 48 h after treatment, stools were formed and oocysts to Cryptosporidium were absent. The patient remained asymptomatic for 3 mo. Hyperimmune bovine colostrum offers an exciting new therapy for cryptosporidiosis; controlled trials to establish efficacy should be undertaken and the active factor(s) characterized.

N. Engl. J. Med. 1988 318: 1240-1243. Volume 318:1240-1243 May 12, 1988 Number 19

Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli

CO Tacket, G Losonsky, H Link, Y Hoang, P Guesry, H Hilpert, and MM Levine

Abstract

Enterotoxigenic Escherichia coli is a common cause of traveler's diarrhea. Prophylaxis against traveler's diarrhea has been associated with side effects from bismuth subsalicylate and the development of resistance to antimicrobial agents. We undertook a double-blind controlled trial in which a bovine milk immunoglobulin concentrate with high titers of antibodies against enterotoxigenic E. coli was used as prophylaxis against E. coli challenge in volunteers. Lyophilized milk immunoglobulins were prepared from the colostrum of cows immunized with several enterotoxigenic E. coli serotypes and fimbria types, E. coli heat-labile enterotoxin, and cholera toxin. As a control, an immunoglobulin concentrate with no anti-E. coli activity was prepared. Ten volunteers received buffered immunoglobulin concentrate against enterotoxigenic E. coli, and 10 received the control immunoglobulin concentrate, dissolved in water, three times a day. No side effects were observed. On the third day of immunoglobulin prophylaxis, the volunteers were given 10(9) colony-forming units of enterotoxigenic E. coli H10407 (O78:H11). This strain produces colonization factor antigen I and heat-labile and heat-stable enterotoxins. None of the 10 volunteers receiving the immunoglobulin concentrate against E. coli had diarrhea, but 9 of the 10 controls did (P less than 0.0001). All volunteers excreted E. coli H10407. We conclude from these preliminary results that milk immunoglobulin concentrate may be an effective prophylaxis against traveler's diarrhea.

Source Information

Department of Medicine, University of Maryland School of Medicine, Baltimore.

The Journal of Nutrition Vol. 127 No. 3 March 1997, pp. 418-426

Suckling Induces Rapid Intestinal Growth and Changes in Brush Border Digestive Functions of Newborn Pigs

Manuscript received 10 June 1996. Initial reviews completed 30 July 1996. Revision accepted 22 November 1996.

Hongzheng Zhang, Christiane Malo*, and Randal K. Buddington

Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762-5759 and * Membrane Transport Research Group, Department of Physiology, B.P. 6128, Succursale Centre-ville, Université de Montréal, Montréal, Québec, Canada H3C3J7

The interplay between suckling, intestinal growth and brush-border membrane functions is critical during the perinatal period. The present study investigates changes in intestinal dimensions, activities of four brush border membrane hydrolases (lactase, sucrase, maltase and aminooligopeptidase) and rates of sugar and amino acid uptake by intact tissues and brush border membrane vesicles during the first 24 h of suckling. Total intestinal weight, mucosal weight and protein content increased 58%, 80% and 126% (P < 0.05) during the first 6 h of suckling; length and surface area did not increase. Total mucosal DNA content was 4.6-fold higher at 24 h after birth, with the rate of increase differing among intestinal regions. Hydrolytic capacities of the entire small intestine increased, more so for homogenates than for brush border membrane vesicles, and more for lactase relative to the other hydrolases studied. Rates of nutrient transport declined, especially for brush border membrane vesicles, for proximal and mid-intestine relative to distal intestine, and for glucose relative to galactose and amino acids. We conclude that 1) changes in brush border membrane digestive functions coincide with rapid intestinal growth, with postnatal patterns varying among hydrolases, transporters and regions; 2) insertion into the brush border membrane, not synthesis, limits the postnatal increase of hydrolase activity; and 3) despite declines in specific activity, hydrolytic and glucose transport capacities of the entire intestine remained stable or increased, and exceeded estimated dietary loads because of intestinal growth.

Key words: colostrum, neonatal, pigs, nutrient transport, brush border hydrolases.

American Journal of Clinical Nutrition, Vol 34, 252-257, Copyright ? 1981 by The American Society for Clinical Nutrition, Inc

ORIGINAL RESEARCH COMMUNICATIONS

Fatty acid composition of human colostrum and mature breast milk

RA Gibson and GM Kneebone

The fatty acid composition of human milk obtained on individual samples from 120 mothers early (day 3 to 5) and later (day 40 to 45) in lactation were determined by argentation thin-layer and gas chromatographic procedures. In comparison with mature milk, human colostrum was characterized by a lower percentage of saturated fatty acids including medium chain length acids, a higher percentage of monounsaturates, and a lower level of linoleic and linolenic acids, but a higher percentage of their long chain polyunsaturated derivatives. It is concluded that in view of their levels in breast milk, the polyenoic derivatives of linoleic and linolenic acids must be taken into account when assessing infant foods.

The Journal of Cell Biology, Vol 72, 617-627, Copyright ? 1977 by The Rockefeller University Press

ARTICLES

Enzymic characteristics of fat globule membranes from bovine colostrum and bovine milk

JT Powell, U Jarlfors and K Brew

Fat globule membranes have been isolated from bovine colostrum and bovine milk by the dispersion of the fat in sucrose solutions at 4 degrees C and fractionation by centrifugation through discontinuous sucrose gradients. The morphology and enzymic characteristics of the separated fractions were examined. Fractions comprising a large proportion of the total extracted membrane were thus obtained having high levels of the Golgi marker enzymes UDP-galactose N- acetylglucosamine beta-4-galactosyltransferase and thiamine pyrophosphatase. A membrane-derived form of the galactosyltransferase has been solubilized from fat and purified to homogeneity. This enzyme is larger in molecular weight than previously studied soluble galactosyltransferases, but resembles in size the galactosyltransferase of lactating mammary Golgi membranes. In contrast, when fat globule membranes were prepared by traditional procedures, which involved washing the fat at higher temperatures, before extraction, galactosyltransferase was not present in the membranes, having been released into supernatant fractions, When the enzyme released by this procedure was partially purified and examined by gel filtration, it was found to be of a degraded form resembling in size the soluble galactosyltransferase of milk. The release is therefore attributed to the action of proteolytic enzymes. Our observations contrast with previous biochemical studies which suggested that Golgi membranes do not contribute to the milk fat globule membrane. They are, however, consistent with electron microscope studies of the fat secretion process, which indicate that secretory vesicle membranes, derived from the Golgi apparatus, may provide a large proportion of the fat globule membrane.

	Laboratory of Colostrum Research