Gut Health

The Application of 

Colostrum in Gut Health

Colostrum is the first milk produced after birth and is particularly rich in immunoglobulins, antimicrobial peptides (eg, lactoferrin and lactoperoxidase), and other bioactive molecules, including growth factors, cytokines and hormones.1 As is the milk that is subsequently produced, colostrum is important for the nutrition, growth, and development of newborns and contributes to the immunologic defense of neonates. Recent studies suggest that bovine colostrum might provide novel treatment options for a variety of gastrointestinal conditions. Some of these are described below:

Infective diarrhea

Most cases of infective diarrhea resolve spontaneously and only occasionally require a short course of antibiotics. For immunocompromised subjects, such as those with HIV infection, prophylaxis against the unusual organisms that they are susceptible to, e.g., Cryptosporidium, may be beneficial. Hyperimmune milk or colostrum preparations have been shown to be of benefit in the prevention and treatment of infection and to increase weight gain in both clinical and veterinary practice, eg, vaccination of cows with specific viruses or bacteria to produce hyperimmune milk has been shown to be beneficial in the prevention and treatment of enteropathic infections due to Escherichia coli and rotavirus.1,2,3 The use of whole hyperimmune colostrum rather than specific antibodies purified from milk or other sources has the added value of potentially stimulating the repair process (due to the presence of growth factors) as well as facilitating the eradication of the infection by mechanisms involving nonspecific antibacterial factors in colostrum and milk.4

Treatment of severe malnutrition and tropical sprue

Severe malnutrition associated with infective diarrhea and atrophy of the intestine (tropical sprue) is a severe life-threatening condition for many parts of the less developed world. Although well defined refeeding regimens are life saving in the majority of cases, there remains a significant number of children who die, despite being placed on these refeeding programs. Various trials to improve mortality figures, including supplementation with colostrum which may help by anti-infective properties, and gut stabilization through its growth factor constituents are currently underway.

Nonsteroidal anti-inflammatory drug–induced gut injury

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and are effective in the treatment of musculoskeletal injury and chronic arthritic conditions. Nevertheless, ≈2% of subjects taking NSAIDs for one year suffer from gastrointestinal adverse effects, including bleeding, perforation, and stricture formation of the stomach and intestine.5 Acid suppressants have been shown to be effective in reducing gastric injury induced by NSAIDs but are less effective in preventing small intestinal injury. Novel therapeutic approaches to deal with these problems, are therefore required and Colostrum has been shown to reduce NSAID-induced small intestinal injury in mice, rats and in human clinical trials.6,7,8

Short-bowel syndrome

Some patients have an insufficient length of bowel to digest and absorb food adequately, usually as a result of massive intestinal resection for vascular insufficiency or after repeated operations for inflammatory bowel disease. Current therapeutic options are unpleasant and associated with a high risk of morbidity or mortality, eg, long-term parenteral (intravenous) feeding and small-bowel transplantation. Strategies to optimize the function of residual bowel and ultimately wean patients off total parenteral nutrition would therefore be of great benefit. There is evidence that individual growth factors or colostrum could be useful in achieving this goal and an example of this are studies showing colostrum supplementation of piglet feeding regimens resulted in a significant increase in intestinal proliferation.9,10 Colostrum supplementation may be of particular value in young children who have undergone intestinal resection because gut adaptation is more likely during early childhood than it is in adulthood.

Chemotherapy-induced mucositis

Current regimens for the treatment of cancers require patients to take much higher doses of chemotherapeutic agents than were used previously. As a result of these higher doses, toxic adverse effects on the bone marrow and gastrointestinal tract can be the factor limiting the dose or duration of treatment. Strategies to protect these tissues and encourage their recovery may facilitate the use of higher doses of chemotherapy, with greater potential for cure. Animal trials have demonstrated the gut protecting effects of colostrum against chemotherapeutic agents and various clinical trials including the use of colostrum are planned or underway.11,12,13

Inflammatory bowel disease

The etiology of ulcerative colitis and Crohn disease is unknown and, therefore, current treatment of these severe, incapacitating conditions has to be on an empiric basis. Studies examining the effect of administration of isolated growth factors such as EGF, PDGF, TGF-β or IGF-I in animal models of colitis have had encouraging results and milk-derived products are already in clinical use for the treatment of inflammatory bowel disease; casein-based enteral feeds are used for the treatment of Crohn disease and their efficacy might be due, in part, to the presence of growth factors in the preparation, which are preserved during the processing of the milk protein.14 In addition, clinical trials of the use of colostrum given by enema have given positive results and studies of oral supplementation of colostrum for inflammatory bowel disease in adults and children are underway.

Necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a severe life-threatening illness of young children that causes severe ulceration of the small and large bowel. Its etiology is unclear, although there are many possible risk factors, including prematurity, enteric infections, intestinal ischemia, and abnormal immune responses. Although many proinflammatory molecules are likely to be involved in the etiology of NEC, there is currently interest in the role of the phospholipid-mediator platelet activating factor (PAF), which is produced by intestinal flora and inflammatory cells during the development of NEC. The finding that human colostrum contains the enzyme PAF acetylhydrolase, which degrades PAF, might therefore be relevant in explaining why human milk feeds protect against the development of NEC.15

Exercise and temperature induced “leaky gut”

‘Leaky gut’ is a condition where the thin mucosal barrier of the gut, which plays a role in absorbing nutrients and preventing large molecules and germs from the gut entering the bloodstream, becomes less effective.

It is a particular problem for those taking part in heavy exercise or who are active in hot conditions. It can lead to ‘heat stroke’ (especially in military personnel deployed to countries with high temperatures) and gut symptoms in athletes.  Recent studies suggest that colostrum given alone or with Zinc carnosine is helpful in preventing the increased gut permeability. These clinical trials were combined with cell culture studies that suggest the colostrum increases the ability of the cells lining the gut to strengthen their connection to neighboring cells, stabilizing the gut lining.16

Summary

The value of colostrum in preventing and treating a multitude of clinical issues is becoming established and the molecular processes underlying these effects are also becoming clearer, strongly suggesting that it is not a single factor but the combination of factors in colostrum that is important. Studies have also shown that the correct preparation of colostrum once collected is important to preserve the biological activity so that it maintains its efficacy when taken by humans. Quality control and evidence-based studies continue to be the cornerstone of effective use of colostrum-based products taken in isolation or in combination with other factors.

References
  1. 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;1:5–14.
  2. Tacket CO, Losonsky G, Link H, et al. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxogenic Escherichia coli. N Engl J Med. 1988;12:1240–1243.
  3. Ebina T, Ohta M, Kanamaru Y, Yamamoto-Osumi Y, and Baba K. Passive immunizations of suckling mice and infants with bovine colostrum containing antibodies to human rotavirus. J Med Virol. 1992;38:117–123.
  4. Sarker SA, Casswall TH, Mahalanabis D, et al. Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum. Pediatr Infect Dis J. 1998;17:1149–1154.
  5. MacDonald TM, Morant SV, Robinson GC, et al. Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study. BMJ. 1997;315:1333–1337.
  6. Zhang S, Lü B, Chao GQ, Chen FM, Chen MY and Chen HQ. [The effects of milk and milk products on non-steroidal anti-inflammatory drug induced intestinal damage in rats]. Zhonghua Nei Ke Za Zhi. 2011 Sep;50:771-775.
  7. Playford RJ, Floyd DN, Macdonald CE, et al. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut. 1999;44:653-658.
  8. Playford RJ, MacDonald CE, Calnan DP, et al. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Clin Sci (Lond). 2001;100:627-633.
  9. Playford RJ, Boulton R, Ghatei MA, et al. Comparison of the effects of TGFα and EGF on gastrointestinal proliferation and hormone release. Digestion. 1996;57:362–367.
  10. Kelly D, King TP, McFadyen M, and Coutts AGP. Effect of preclosure colostrum intake on the development of the intestinal epithelium of artificially reared piglets. Biol Neonate. 1993;64:235–244.
  11. Hirano M, Iweakiri R, Fujimoto K, et al. Epidermal growth factor enhances repair of rat intestinal mucosa damaged after oral administration of methotrexate. J Gastroenterol. 1995;30:169–176.
  12. Sonis ST, Lindquist L, Van Vugt A, et al. Prevention of chemotherapy-induced ulcerative mucositis by transforming growth factor beta 3. Cancer Res. 1994;54:1135–1138.
  13. Howarth GS, Francis GL, Cool JC, Ballard RW, Read LC. Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats. J Nutr. 1996;126:2519–2530.
  14. Procaccino F, Reinshagen M, Hoffman P, et al. Protective effect of epidermal growth factor in an experimental model of colitis. Gastroenterology. 1994;107:12–17.
  15. Moya FR, Eguchi H, Zhao B, et al. Platelet-activating factor acetylhydrolase in term and preterm human milk: a preliminary report. J Pediatr Gastroenterol Nutr. 1994;19:236–239.
  16. Davison G, Marchbank T, March DS, Thatcher R, and Playford RJ. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. Am J Clin Nutr. 2016;104:526-536.

Gut Health

The Application of 

Colostrum in Gut Health

Colostrum is the first milk produced after birth and is particularly rich in immunoglobulins, antimicrobial peptides (eg, lactoferrin and lactoperoxidase), and other bioactive molecules, including growth factors, cytokines and hormones.1 As is the milk that is subsequently produced, colostrum is important for the nutrition, growth, and development of newborns and contributes to the immunologic defense of neonates. Recent studies suggest that bovine colostrum might provide novel treatment options for a variety of gastrointestinal conditions. Some of these are described below:

Infective diarrhea

Most cases of infective diarrhea resolve spontaneously and only occasionally require a short course of antibiotics. For immunocompromised subjects, such as those with HIV infection, prophylaxis against the unusual organisms that they are susceptible to, e.g., Cryptosporidium, may be beneficial. Hyperimmune milk or colostrum preparations have been shown to be of benefit in the prevention and treatment of infection and to increase weight gain in both clinical and veterinary practice, eg, vaccination of cows with specific viruses or bacteria to produce hyperimmune milk has been shown to be beneficial in the prevention and treatment of enteropathic infections due to Escherichia coli and rotavirus.1,2,3 The use of whole hyperimmune colostrum rather than specific antibodies purified from milk or other sources has the added value of potentially stimulating the repair process (due to the presence of growth factors) as well as facilitating the eradication of the infection by mechanisms involving nonspecific antibacterial factors in colostrum and milk.4

Treatment of severe malnutrition and tropical sprue

Severe malnutrition associated with infective diarrhea and atrophy of the intestine (tropical sprue) is a severe life-threatening condition for many parts of the less developed world. Although well defined refeeding regimens are life saving in the majority of cases, there remains a significant number of children who die, despite being placed on these refeeding programs. Various trials to improve mortality figures, including supplementation with colostrum which may help by anti-infective properties, and gut stabilization through its growth factor constituents are currently underway.

Nonsteroidal anti-inflammatory drug–induced gut injury

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and are effective in the treatment of musculoskeletal injury and chronic arthritic conditions. Nevertheless, ≈2% of subjects taking NSAIDs for one year suffer from gastrointestinal adverse effects, including bleeding, perforation, and stricture formation of the stomach and intestine.5 Acid suppressants have been shown to be effective in reducing gastric injury induced by NSAIDs but are less effective in preventing small intestinal injury. Novel therapeutic approaches to deal with these problems, are therefore required and Colostrum has been shown to reduce NSAID-induced small intestinal injury in mice, rats and in human clinical trials.6,7,8

Short-bowel syndrome

Some patients have an insufficient length of bowel to digest and absorb food adequately, usually as a result of massive intestinal resection for vascular insufficiency or after repeated operations for inflammatory bowel disease. Current therapeutic options are unpleasant and associated with a high risk of morbidity or mortality, eg, long-term parenteral (intravenous) feeding and small-bowel transplantation. Strategies to optimize the function of residual bowel and ultimately wean patients off total parenteral nutrition would therefore be of great benefit. There is evidence that individual growth factors or colostrum could be useful in achieving this goal and an example of this are studies showing colostrum supplementation of piglet feeding regimens resulted in a significant increase in intestinal proliferation.9,10 Colostrum supplementation may be of particular value in young children who have undergone intestinal resection because gut adaptation is more likely during early childhood than it is in adulthood.

Chemotherapy-induced mucositis

Current regimens for the treatment of cancers require patients to take much higher doses of chemotherapeutic agents than were used previously. As a result of these higher doses, toxic adverse effects on the bone marrow and gastrointestinal tract can be the factor limiting the dose or duration of treatment. Strategies to protect these tissues and encourage their recovery may facilitate the use of higher doses of chemotherapy, with greater potential for cure. Animal trials have demonstrated the gut protecting effects of colostrum against chemotherapeutic agents and various clinical trials including the use of colostrum are planned or underway.11,12,13

Inflammatory bowel disease

The etiology of ulcerative colitis and Crohn disease is unknown and, therefore, current treatment of these severe, incapacitating conditions has to be on an empiric basis. Studies examining the effect of administration of isolated growth factors such as EGF, PDGF, TGF-β or IGF-I in animal models of colitis have had encouraging results and milk-derived products are already in clinical use for the treatment of inflammatory bowel disease; casein-based enteral feeds are used for the treatment of Crohn disease and their efficacy might be due, in part, to the presence of growth factors in the preparation, which are preserved during the processing of the milk protein.14 In addition, clinical trials of the use of colostrum given by enema have given positive results and studies of oral supplementation of colostrum for inflammatory bowel disease in adults and children are underway.

Necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a severe life-threatening illness of young children that causes severe ulceration of the small and large bowel. Its etiology is unclear, although there are many possible risk factors, including prematurity, enteric infections, intestinal ischemia, and abnormal immune responses. Although many proinflammatory molecules are likely to be involved in the etiology of NEC, there is currently interest in the role of the phospholipid-mediator platelet activating factor (PAF), which is produced by intestinal flora and inflammatory cells during the development of NEC. The finding that human colostrum contains the enzyme PAF acetylhydrolase, which degrades PAF, might therefore be relevant in explaining why human milk feeds protect against the development of NEC.15

Exercise and temperature induced “leaky gut”

‘Leaky gut’ is a condition where the thin mucosal barrier of the gut, which plays a role in absorbing nutrients and preventing large molecules and germs from the gut entering the bloodstream, becomes less effective.

It is a particular problem for those taking part in heavy exercise or who are active in hot conditions. It can lead to ‘heat stroke’ (especially in military personnel deployed to countries with high temperatures) and gut symptoms in athletes.  Recent studies suggest that colostrum given alone or with Zinc carnosine is helpful in preventing the increased gut permeability. These clinical trials were combined with cell culture studies that suggest the colostrum increases the ability of the cells lining the gut to strengthen their connection to neighboring cells, stabilizing the gut lining.16

Summary

The value of colostrum in preventing and treating a multitude of clinical issues is becoming established and the molecular processes underlying these effects are also becoming clearer, strongly suggesting that it is not a single factor but the combination of factors in colostrum that is important. Studies have also shown that the correct preparation of colostrum once collected is important to preserve the biological activity so that it maintains its efficacy when taken by humans. Quality control and evidence-based studies continue to be the cornerstone of effective use of colostrum-based products taken in isolation or in combination with other factors.

References
  1. 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;1:5–14.
  2. Tacket CO, Losonsky G, Link H, et al. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxogenic Escherichia coli. N Engl J Med. 1988;12:1240–1243.
  3. Ebina T, Ohta M, Kanamaru Y, Yamamoto-Osumi Y, and Baba K. Passive immunizations of suckling mice and infants with bovine colostrum containing antibodies to human rotavirus. J Med Virol. 1992;38:117–123.
  4. Sarker SA, Casswall TH, Mahalanabis D, et al. Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum. Pediatr Infect Dis J. 1998;17:1149–1154.
  5. MacDonald TM, Morant SV, Robinson GC, et al. Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study. BMJ. 1997;315:1333–1337.
  6. Zhang S, Lü B, Chao GQ, Chen FM, Chen MY and Chen HQ. [The effects of milk and milk products on non-steroidal anti-inflammatory drug induced intestinal damage in rats]. Zhonghua Nei Ke Za Zhi. 2011 Sep;50:771-775.
  7. Playford RJ, Floyd DN, Macdonald CE, et al. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut. 1999;44:653-658.
  8. Playford RJ, MacDonald CE, Calnan DP, et al. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Clin Sci (Lond). 2001;100:627-633.
  9. Playford RJ, Boulton R, Ghatei MA, et al. Comparison of the effects of TGFα and EGF on gastrointestinal proliferation and hormone release. Digestion. 1996;57:362–367.
  10. Kelly D, King TP, McFadyen M, and Coutts AGP. Effect of preclosure colostrum intake on the development of the intestinal epithelium of artificially reared piglets. Biol Neonate. 1993;64:235–244.
  11. Hirano M, Iweakiri R, Fujimoto K, et al. Epidermal growth factor enhances repair of rat intestinal mucosa damaged after oral administration of methotrexate. J Gastroenterol. 1995;30:169–176.
  12. Sonis ST, Lindquist L, Van Vugt A, et al. Prevention of chemotherapy-induced ulcerative mucositis by transforming growth factor beta 3. Cancer Res. 1994;54:1135–1138.
  13. Howarth GS, Francis GL, Cool JC, Ballard RW, Read LC. Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats. J Nutr. 1996;126:2519–2530.
  14. Procaccino F, Reinshagen M, Hoffman P, et al. Protective effect of epidermal growth factor in an experimental model of colitis. Gastroenterology. 1994;107:12–17.
  15. Moya FR, Eguchi H, Zhao B, et al. Platelet-activating factor acetylhydrolase in term and preterm human milk: a preliminary report. J Pediatr Gastroenterol Nutr. 1994;19:236–239.
  16. Davison G, Marchbank T, March DS, Thatcher R, and Playford RJ. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. Am J Clin Nutr. 2016;104:526-536.