Gut Health

Beneficial Bioactives

Found in Colostrum

While bovine colostrum has been used for thousands of years in human medicine, its components also offer an ideal bioactive backbone for developing new oral therapeutics that can modulate our gut and systemic biology. Below is an overview of the components of colostrum and their potential therapeutic benefit.

Gut Health

Beneficial Bioactives

Found in Colostrum

While bovine colostrum has been used for thousands of years in human medicine, its components also offer an ideal bioactive backbone for developing new oral therapeutics that can modulate our gut and systemic biology. Below is an overview of the components of colostrum and their potential therapeutic benefit.

Immune Factors

Immunoglobulins
  • Colostrum contains IgG, IgA, IgM, IgD, IgE1
  • These immunoglobulins naturally target a range of human pathogens, including Rotavirus, Shigella, Escherichia coli, Salmonella, and other viral and bacterial pathogens and multicellular parasites
  • The immunoglobulins in colostrum can be further enhanced to target additional pathogens through vaccinating donor animals which provide hyperimmunized colostrum
Cytokines
  • Colostrum contains numerous cytokines including IL-1β, IL-6, TNF-α, IFN-γ, and IL-1ra2
  • These small peptide molecules are important mediators in the regulation of immune and inflammatory responses3
  • In the newborn, cytokines play an important role in combination with the ingested maternal immunoglobulins and non-specific antibacterial components of colostrum4
  • They are major regulators of epithelial cell growth and development, including intestinal inflammation and epithelial restitution following mucosal damage5

Broad Spectrum Antimicrobials

Lactoferrin
  • Lactoferrin is an 80 kDa iron-binding glycoprotein with antiviral and antimicrobial activity
  • Shown to inhibit the growth of specific microbes including Escherichia coli, Salmonella typhimurium, Shigella, dysenteria, and Streptococcus mutans6,7,8
  • Antiviral effects against herpes simplex virus type-1 (HSV-1), human immunodeficiency virus-1 (HIV-1) and human cytomegalovirus9,10
  • Plays an important role in iron uptake in the intestine and in the activation of phagocytes and immune responses3
  • Immune mediator regulating target cells responses, including those involved in oxidative stress and systematic inflammatory responses
  • Clinical studies show lactoferrin can inactivate LPS and inhibit dermal inflammatory cytokine production, indicating lactoferrin may have a potent anti-inflammatory effect11
Lysozyme
  • An enzyme that helps to support immune function by attacking specific bacteria and fungi
  • Lysozyme interacts with other components in colostrum, like lactoperoxidase, lactoferrin and IgA, resulting in a synergistic blend of antimicrobials3
  • The natural substrate of this enzyme is the peptidoglycan layer of the bacterial cell wall and its degradation results in the lysis (breaking down of the cell wall) of the bacteria12
Lactoperoxidase
  • A major antibacterial enzyme found in colostrum
  • Primary function is in the defense against microbial infection
  • Next to its antimicrobial and antiviral activity, degradation of various carcinogens and protection of animal cells against peroxidative effects have been reported13
  • Inhibits bacterial metabolism via the oxidation of essential sulfhydryl groups in proteins14
  • Shown to inactivate polio virus, vaccinia virus, and HIV-13715,16

Growth and Repair Factors

Insulin-like Growth Factors (IGF-I and IGF-II)
  • The most abundant growth factors in colostrum
  • Primary structures are highly conserved across species and have identical sequences in humans17
  • Heat and acid stable and widely distributed mediators of cell growth, development, and differentiation18
  • Amino acid sequence of purified bovine IGF-I is identical to that of human IGF-I19,20
  • Dietary IGF-I can stimulate cell proliferation in the gastrointestinal tract21,22
  • Dietary IGFs may have a direct effect on the epithelial cells of the gastrointestinal tract and can be absorbed into circulation23
Epidermal Growth Factor (EGF)
  • Plays an important role in the regulation of cell growth, proliferation and differentiation
  • Stimulates the repair process at the site of inflammation24
  • Plays an important role in preventing bacterial translocation and stimulating gut immunity25,26
  • Anabolic growth factor with possible differentiation-inducing factors for intestinal epithelium of newborns, suggesting possible applications of recombinant IGF and IGF analogs for repair of damaged gastrointestinal tissues27
  • Supplementation with EGF may aid in the recovery of traumatized gastric and intestinal tissues28
Transforming Growth Factor Alpha (TGF-α)
  • Plays a complementary role with TGF-β in controlling the balance between cell proliferation and differentiation in the intestinal epithelium4,29
  • Systematic administration of TGF-α stimulates gastrointestinal growth and repair, inhibits acid secretion, stimulates mucosal restitution after injury and increases gastric mucin concentrations30
  • Upregulation of TGF-α expression has been shown to occur in the gastrointestinal mucosa at sites of injury, supporting a role of TGF-α in mucosal growth and repair31
  • Major physiological role of TGF-α is to act as a mucosal-integrity peptide, maintaining normal epithelia function in the non-damaged mucosa32
Transforming Growth Factor Beta (TGF-β)
  • Plays an important role on the regulation of the immune system23
  • Stimulates proliferation of some cells, especially in connective tissue, whereas it acts as a growth inhibitor for other cells3
  • During injury or disease, it acts in concert with EGF to stimulate cell proliferation33
  • Key player in stimulating restitution, the early phase of the repair process during which surviving cells from the edge of a wound migrate over the denuded area to reestablish epithelial continuity4
  • TGF-β blocks the destruction of newly synthesized cells by regulating the synthesis of proteases
  • Both TGF-α and TGF-β are helpful in the repair and integrity of epithelium of the gastrointestinal tract24
Oligosaccharides and Glycoconjugates
  • Oligosaccharides are defined as carbohydrates which contain between three and ten monosaccharide residues, covalently linked through glycosidic bonds and are divided into two broad classes, neutral and acidic34
  • Oligosaccharides act as a prebiotic as they are neither digested nor absorbed in the upper intestinal tract of humans but are delivered intact into the colon where they can act as nutrients for colonic microflora34
  • Specific oligosaccharides support the growth of beneficial bacteria and modulate the microbiome35
  • Oligosaccharides and glycoconjugates in milk and colostrum are soluble receptor analogues of epithelial cell-surface carbohydrates and can therefore compete with virulent bacteria and viruses for attachment sites34
  • Sialylated oligosaccharides have been shown to inhibit binding of pathogenic strains of Escherichia coli in neonates and many other pathogens36,37
  • Adhesion to epithelial cells by ulcer-causing human pathogen Heliobacter pylori is inhibited by sialylated oligosaccharides38

References

  1. McGrath, BA, Fox, PF, McSweeney, PLH, and Kelly, AL. Composition and properties of bovine colostrum: A review. Dairy Sci. Technol. 2016;96:133–158.
  2. Hagiwara K, Kataoka S, Yamanaka H, Kirisawa R, and Iwai H. Detection of cytokines in bovine colostrum. Vet Immunol Immunopathol. 2000;76:183–190.
  3. Boudry C, Dehoux JP, Portetelle D and Buldgen A. Bovine colostrum as a natural growth promoter of newly weaned piglets: a  review. Biotechnol Agron Soc Environ. 2008;12:157–170.
  4. Playford RJ,  Macdonald CE, and Johnson WS. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. Am J Clin Nutr. 2000;72:5–14.
  5. Elson CO and Beagley KW. Cytokines and immune mediators. In: Johnson L.R. Physiology of the gastro-intestinal tract. 3rd ed. New York, USA: Raven, 1994, 243–266.
  6. Rainard P. Bcteriostatic activity of bovine milk lactoferrin against mastitic bacteria.
    Vet Microbiol. 1986;11:387–392.
  7. Batish VK, Chander H, Zumdegni KC, Bhatia KL, and Singh RS. Antibacterial activity of lactoferrin against some common food-borne pathogenic organisms. Aust. J. Dairy Technol. 1988;43:16–18.
  8. Lassiter MO, Newsome AL, Sams LD, and Arnold RR. Characterization of lactoferrin interaction with Streptococcus mutans. J Dent Res. 1987;66:480–485.
  9. Fujihara T and Hayashi K. Lactoferrin inhibits herpes simplex virus type-1 (HSV-1) infection  to mouse cornea. Arch Virol. 1995;140:1469–1472.
  10. Harmsen MC, Swart PJ, de Béthune MP, et al. Antiviral effects of plasma and milk proteins: Lactoferrin shows potent  activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J Infect Dis. 1995;172:380–388.
  11. Cohen MS, Mao J, Rasmussen GT, Serody JS, and Britigan BE. Interaction of lactoferrin and lipopolysaccharide (LPS): effects of the  antioxidant property of lactoferrin and the ability of LPS to prime human neutrophils for enhanced  superoxide formation. J Infect Dis. 1992;166:1375–1378.
  12. Reiter B. Review of the progress of dairy science: Antimicrobial systems in milk. Journal of  Dairy Research. J Dairy Res. 1987;45:131–147.
  13. Kussendrager KD and van Hooijdonk ACM. Lactoperoxidase: physic-chemical properties,  occurrence, mechanism of action and applications. Brit J Nutr. 2000;84:19–25.
  14. Pruitt KM and Reiter B. Biochemistry of peroxidase system. In The Lactoperoxidase System:  Chemistry and Biological Significance; Pruitt KM; Tnovuo J; Eds; Marcel Dekker: New York, USA: 1985,143–178.
  15. Belding ME, Klebanoff SJ, and Ray CG. Peroxidase-mediated virucidal systems. Science. 1970;9:195–196.
  16. Yamaguchi Y, Semmel M, Stanislawski L, Strosberg AD, and Stanislawski M. Virucidal effects of glucose oxidase and peroxidase or their protein  conjugates on human immunodeficiency virus type 1. Antimicrob Agents Chemother. 1993;37:26–31.
  17. Xu RJ, Wang F, and Zhang SH. Postnatal adaptation of the gastro-intestinal tract in neonatal pigs: a possible  role of milk-borne growth factors. Livest Prod Sci. 2000;66:95–107.
  18. Pakkanen R and Aalto J. Growth factors and antimicrobial factors of bovine colostrum. Int Dairy J. 1997;7:285–297.
  19. Francis GL, Upton FM, Ballard FJ, McNeil KA, and Wallace JC. Insulin-like growth factors 1 and 2 in bovine colostrum. Biochem J. 1988;251: 95–103.
  20. Marcotty C, Frankenne F, Van Beeumen J, Maghuin-Rogister G, and Hennen G. Insulin-like growth factor (IGF-1) from cow colostrum: Purification and characterization. Growth Regul. 1991;1:56–61.
  21. Xu RJ, Mellor DJ, Birtles MJ, Breier BH, and Gluckman PD. Effects of oral IGF-I or IGF-II on digestive organ growth in newborn piglets. Biol Neonate. 1994;66:280–287.
  22. CR Baumrucker and Blum JW. (1993) Secretion of insulin-like growth factors in milk and their effects on the neonate. Livest Prod Sci. 1993;35: 49–72.
  23. Tripathi V and Vashishtha B. Bioactive compounds of colostrum and its application. Food Res Int. 2006;22:225–244.
  24. Rawal P, Gupta V, and Thapa BR. Role of colostrum in gastrointestinal infections. Indian J Pediatr. 2008;75: 917–921.
  25. Okuyama H, Urao M, Lee D, Drongowski RA, and Coran AG. The effect of epidermal growth factor on bacterial translocation in newborn rabbits. J Pediatr Surg. 1998;33:225–228.
  26. Thapa BR. Health factors in colostrum. Indian J Pediatr. 2005;72:579–581.
  27. Simmen FA, Badinga L, Green ML, Kwak I, Song S, and Simmen RC. The porcine insulin-like growth factor system: at the interface of nutrition, growth and reproduction. J Nutr. 1998;128(2 Suppl):315S–320S.
  28. Jaeger LA, Lamar CH, Cline TR, and Cardona CJ. Effect of orally administered epidermal growth factor on the jejunal mucosa  of weaned piglets. Am J Vet Res. 1990;51:471–474.
  29. Kingsnorth AN, Vowles R, and Nash JR. Epidermal growth factor increases tensile strength in intestinal wounds in pigs. Br J Surg. 1990;77:409–412.
  30. Barnard JA, Beauchamp RD, Russell WE, Dubois RN, and Coffey RJ. Epidermal growth factor-related peptides and their relevance to  gastrointestinal pathophysiology. Gastroenterology. 1995;108:564–580.
  31. Coffey RJ, Romano M, and Goldenring J. Roles for transforming growth factor-alpha in the stomach. J Clin Gastroenterol. 1995;21(Suppl 1):S36-S39.
  32. Playford RJ. Peptides and gastrointestinal mucosal integrity. Gut. 1995;37: 595–597.
  33. Border WA and Noble NA. Targeting TGF-β for treatment of disease. Nat Med. 1995;1:1000–1001.
  34. Gopal PK and Gill HS. Oligosaccharides and glycoconjugates in bovine milk and colostrum. Br J Nutr. 2000;84 Suppl 1:S69–S74.
  35. Azcarate-Peril MA, Ritter AJ, and Savaiano D, et al. Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals. Proc Natl Acad Sci USA. 2017;114:E367–E375.
  36. Parkkinen J and Finne J. Occurrence of N-acetylglucosamine 6-phosphate in complex carbohydrates. Characterisation of a phosphorylated sialyl oligosaccharide from bovine colostrum. J Biol Chem. 1985;260:10971–10975.
  37. Korhonen TK, Valtonen MV, and Parkkinen J, et al. Serotypes, hemolysin production, and receptor recognition of Escherichia  coli strains associated with neonatal sepsis and meningitis. Infect Immun. 1985;48:486–491.
  38. Simon PM, Goode PL, Mobasseri A, and Zopf D. Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by sialic acid-containing oligosaccharides. Infect Immun. 1997;65:750–757.