[i] Playford, RJ, et al.  Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. American Journal of Clinical Nutrition 72(1):5-14 (2000).  Colostrum is the specific first diet of mammalian neonates and is rich in immunoglobulins, antimicrobial peptides, and growth factors. In this article we review some of these constituents of human and bovine colostrum in comparison with those of mature milk. Recent studies suggest that colostral fractions, or individual peptides present in colostrum, might be useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease, nonsteroidal anti-inflammatory drug-induced gut injury, and chemotherapy-induced mucositis. We therefore discuss the therapeutic possibilities of using whole colostrum, or individual peptides present in colostrum, for the treatment of various gastrointestinal diseases and the relative merits of the 2 approaches.

[ii] Baglioni, T, Fioretti, C.  [Serum immunoglobulins in colostrum and cow's milk studied by the immunoelectrophoretic method]. Archivio Veterinario Italiano 18(6):419-427 (1967).  Both IgG and IgM identified in bovine colostrum using immunoelectrophoresis.

[iii] Mickelson, KN, Moriarty, KM.  Immunoglobulin levels in human colostrum and milk. Journal of Pediatric Gastroenterology and Nutrition 1(3):381-384 (1982).  Levels of sIgA, IgG and IgM were determined in human colostrum and milk.  A mean concentration of 32 g/L was found for sIgA (1.5-83.7 g/L), 1.13 g/L for IgM and 0.53 g/L for IgG.  While total amounts declined with time postpartum, relative proportions remained the same.

[iv] Korhonen, H, et al.  Bovine milk antibodies for health.  British Journal of Nutrition 84(Suppl.1):S135-S146 (2000).  Bovine colostrum provides safe, effective protection against many pathogens.

[v] Korhonen H, et al.  Bactericidal effect of bovine normal and immune serum, colostrum and milk against Helicobacter pylori. Journal of Applied Bacteriology 78:655-662 (1995).  Helicobacter pylori is a major cause of gastritis and ulcers in humans.  Serum and colostrum from non-immunized Friesian cows were found to be highly bactericidal against H. pylori.  Post-colostral milk did not show any bactericidal effect against H. pylori.

[vi] Bitzan, MM, et al.  Inhibition of Helicobacter pylori and Helicobacter mustelae binding to lipid receptors by bovine colostrum. Journal of Infectious Diseases 177:955-961 (1998).

[vii] Ogra, PL, et al.  Colostrum-derived immunity and maternal-neonatal interaction. Annals of the New York Academy of Sciences 409:82-95 (1983).  Peyer’s patches are found throughout the intestinal tract, and groups of similar immunoactive cells are found in the bronchial mucosa. Both the intestinal and bronchial immunoactive cell groups respond to allergens, antigens and pathogens by neutralizing or destroying them.  In newborns, these special cell groups are not immediately operative but protection is provided by a variety of immune factors from the mother’s colostrum. Antibodies found in colostrum protect against Eschericia coli, Salmonella, Shigella, Vibrio cholera, Bacteriodes fragilis, Streptococcus pneumoniae, Bordtella pertussis, Clostridium diphtheria, Clostridium tetani, Streptococcus mutans and Candida albicans.

[viii] Kim, K, et al.  In vitro and in vivo neutralizing activity of human colostrum and milk against purified toxins A and B of Clostridium difficile. Journal of Infectious Disease 150(1):57-62 (1984).  Both colostrum and mature milk had activity against Clostridium difficile toxins A and B.

[ix] Warny, M, et al.  Bovine immunoglobulin concentrate-clostridium difficile retains C difficile toxin neutralizing activity after passage through the human stomach and small intestine. Gut 44(2):212-217 (1999).  Both antibiotic activity against C. difficile and toxin neutralizing activity of a bovine immunoglobulin concentrate survived passage through the stomach and small intestine, indicating that these antibodies retain potency throughout the gastrointestinal tract.

[x] Bellamy, W, et al.  Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin. Journal of Applied Bacteriology 73(6):472-479 (1992).  Lactoferricin B, a fragment of bovine lactoferrin, which is one of the principal components of the innate immune system found in colostrum, showed strong bactericidal effects on a broad spectrum of gram-positive and gram-negative bacteria, including Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, Campylobacter jejuni, Staphylococcus aureus, Streptococcus mutans, Corynebacterium diphtheriae, Listeria monocytogenes and Clostridium perfringens.

[xi] Hagiwara, K, et al.  Detection of cytokines in bovine colostrum. Veterinary Immunology and Immunopathology 76:183-190 (2000).  Colostrum contains five cytokines, TNF-α, IL-1β, IL-6, IL-1ra (receptor antagonist) and INF-γ, which have known immunomodulatory effects.

[xii] Bühler, C., et al.  Small intestinal morphology in eight-day-old calves fed colostrum for different durations or only milk replacer and treated with long-R3-insulin-like growth factor I and growth hormone. Journal of Animal Science 76:758-765 (1998).

[xiii] Pluske, JR, Morel, PCH.  Increasing weaner pig productivity in New Zealand pig herds. Unpublished research (1999).  Piglets fed a liquid supplement with colostrum powder had a marked increase in villi height in the lumen of the small intestine, indicating greater digestion and absorption of nutrients.  There were also an increased number of immune cells in the villi, indicating enhanced immune competency.

[xiv] Blättler, U, et al.  Feeding colostrum, its composition and feeding duration variably modify proliferation and morphology of the intestine and digestive enzyme activities of neonatal calves. Journal of Nutrition 131(4):1256-1263 (2001).

[xv] Prosser, C, et al.  Reduction in heat induced gastrointestinal hyperpermeability in rats by bovine colostrum and goat milk powders. Journal of Applied Physiology 96:650-654 (2004).

[xvi] Playford RJ, et al.  Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut 44:653-658 (1999).

[xvii] Farhadi, A, et al.  Intestinal barrier: An interface between health and disease. Journal of Gastroenterology and Hepatology 18(5):479-497 (2003).  An intact intestinal barrier is essential to maintaining health and preventing tissue injury and disease.  Hyperpermeability of this barrier is believed to contribute to the pathogenesis of several gastrointestinal disorders including inflammatory bowel disease, celiac disease and food allergy.

[xviii] Hamilton, I, et al.  Small intestinal permeability in dermatological disease. Quarterly Journal of Medicine 56(221):59-567 (1985).  Abnormal intestinal permeability was found in 62 cases of atopic dermatitis, 29 cases of psoriasis, and 18 cases of dermatitis herpetiformis, all autoimmune conditions.

[xix] Katz, KD, Hollander, D. Intestinal mucosal permeability and rheumatological diseases. Baillieres Clinical Rheumatology 3(2):271-284 (1989).  Rheumatological disorders frequently have gastrointestinal manifestations and, conversely, intestinal disorders frequently have rheumatological manifestations. The possibility of altered intestinal permeability in arthritic patients may provide the bridge needed to link the two organ systems. The normal intestine absorbs nutrients and excludes the remaining material. If the intestine were less discriminating or 'leaky' then material normally excluded would be able to cross the intestinal mucosa into the lamina propria. An inflammatory response to these antigens, be they dietary, bacterial, or viral in origin, could produce either local or systemic disease. This would depend upon the type of immunological response and the cross-reactivity between the host's antigens and the absorbed antigens. This theory could account for the postulated relationship between intestinal abnormalities and the pathogenesis of some forms of arthritis.

[xx] Yacyshyn, B, et al.  Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Digestive Diseases and Sciences 41(12):2493-2498 (1998).

[xxi] Fresko, I, et al.  Intestinal permeability in Behçet's syndrome. Annals of Rheumatic Disease 60(1):65-66 (2001).  The intestinal permeability was measured in patients with Behçet's syndrome and compared with normal controls.  Those with Behçet's had significantly greater permeability compared to controls.

[xxii] Hollander, D.  Intestinal permeability, leaky gut, and intestinal disorders. Current Gastroenterology Reports 1(5):410-416 (1999).  Patients with Crohn’s disease have abnormally increased permeability in their gastrointestinal tract.

[xxiii] Meddings, JB, et al.  Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. American Journal of Physiology 276(4 part1):G951-G957 (1999).  The appearance of increased gastrointestinal permeability preceded the appearance of disease symptoms in spontaneously diabetic rats.  This is also true in celiac disease and Crohn's disease.

[xxiv] Galland, L.  Intestinal Parasites, Bacterial Dysbiosis and Leaky Gut. In: Power Healing, Random House, 1998.  Leaky gut syndrome is associated with chronic fatigue syndrome.

[xxv] Teitelbaum, JE, Walker, WA.  Nutritional impact of pre- and probiotics as protective gastrointestinal organisms. Annual Review of Nutrition 22:107-138 (2002).  The health benefits of pre- and probiotics have been the subject of increased research interests. These food supplements have been demonstrated to alter the pre-existing intestinal flora so as to provide an advantage to the host. This review focuses on the scientific evidence both for and against their role in promoting health and treating disease. Specific attention is turned to their effects on immunomodulation, lipid metabolism, cancer prevention, diarrhea, Helicobacter pylori, necrotizing enterocolitis, allergy, and inflammatory bowel disease.

[xxvi] Tejada-Simon, MV, et al.  Ingestion of yogurt containing Lactobacillus acidophilus and Bifidobacterium to potentiate immunoglobulin A responses to cholera toxin in mice. Journal of Dairy Science 82(4):649-660 (1999).  Lactic acid bacteria have been reported to have benefits for the prevention and treatment of some forms of diarrhea and related conditions.  This study showed that feeding yogurt supplemented with Lactobacillus and Bifidobacterium enhanced IgA responses to cholera toxin.

[xxvii] Gibson, GR, et al.  Prebiotics and resistance to gastrointestinal infections. British Journal of Nutrition 93(Suppl. 1):S31-S34 (2005).  Acute gut disorder is a cause for significant medicinal and economic concern. Certain individual pathogens of the gut, often transmitted in food or water, have the ability to cause severe discomfort. There is a need to manage such conditions more effectively. The route of reducing the risk of intestinal infections through diet remains largely unexplored. Antibiotics are effective at inhibiting pathogens; however, these should not be prescribed in the absence of disease and therefore cannot be used prophylactically. Moreover, their indiscriminate use has reduced effectiveness. Evidence has accumulated to suggest that some of the health-promoting bacteria in the gut (probiotics) can elicit a multiplicity of inhibitory effects against pathogens. Hence, an increase in their numbers should prove effective at repressing pathogen colonization if/when infectious agents enter the gut. As such, fortification of indigenous bifidobacteria/lactobacilli by using prebiotics should improve protection. There are a number of potential mechanisms for lactic acid bacteria to reduce intestinal infections. Firstly, metabolic end products such as acids excreted by these micro-organisms may lower the gut pH to levels below those at which pathogens are able to effectively compete. Also, many lactobacilli and bifidobacteria species are able to excrete natural antibiotics, which can have a broad spectrum of activity. Other mechanisms include an improved immune stimulation, competition for nutrients and blocking of pathogen adhesion sites in the gut. Many intestinal pathogens like type 1 fimbriated Escherichia coli, salmonellae and campylobacters utilize oligosaccharide receptor sites in the gut. Once established, they can then cause gastroenteritis through invasive and/or toxin forming properties. One extrapolation of the prebiotic concept is to simulate such receptor sites in the gut lumen. Hence, the pathogen is 'decoyed' into not binding at the host mucosal interface. The combined effects of prebiotics upon the lactic acid flora and anti-adhesive strategies may lead towards new dietary interventions against food safety agents.

[xxviii] Agerholm-Larsen, L, et al.  Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases. European Journal of Clinical Nutrition 54(4):288-297 (2000).  In an 8 week randomized, double-blind trial, 70 healthy but overweight subjects were given yogurt with probiotic cultures.  LDL-cholesterol was significantly decreased (8.4%) over control and blood pressure was lowered.  Fibrinogen levels were also increased, suggesting improved clotting function.

[xxix] Gopal, PK, Gill, HS.  Oligosaccharides and glycoconjugates in bovine milk and colostrum. British Journal of Nutrition 84(Suppl. 1):S69-S74 (2000).  Oligosaccharides and glycoconjugates are some of the most important bioactive components in milk. A great deal of information is available on the biological function of the components from human milk. Their primary role seems to be in providing protection against pathogens by acting as competitive inhibitors for the binding sites on the epithelial surfaces of the intestine. Evidence is also available to support the role of some of these components as growth promoters for genera of beneficial microflora in the colon. Compared with human milk, levels of oligosaccharides in bovine milk are very low. Nevertheless, a number of neutral and acidic oligosaccharides have been isolated from bovine milk and characterized. The highest concentration of these molecules is found in early post-parturition milk (colostrum). The chemical structure of the oligosaccharides and many of the glycoconjugates from bovine milk are similar to those in human milk. It is likely that bovine oligosaccharides and glycoconjugates can be used in milk products as bioactive components in human nutrition.

[xxx] Guarner, F.  Inulin and oligofructose: impact on intestinal diseases and disorders. British Journal of Nutrition 93(Suppl. 1):S61-S65 (2005).  A large and diverse variety of bacteria have evolved and adapted to live in the human intestinal habitat in a symbiotic arrangement that influences both physiology and pathology in the host. Symbiosis between host and flora can be optimized by prebiotics. Inulin-type fructans have been shown to improve the metabolic functions of the commensal flora. Clinical and experimental data suggest that they also improve the gut mucosal barrier. Furthermore, modulation of the trophic functions of the flora by these prebiotics could help in the prevention of inflammatory bowel diseases. The anti-inflammatory effects of inulin or oligofructose have been assessed in the rat model of distal colitis induced by dextran sodium sulphate, which histologically resembles human ulcerative colitis, and in the trinitrobenzene sulphonic acid model that resembles human Crohn's disease. Both inulin and oligofructose stimulate colonic production of SCFA and favor the growth of indigenous lactobacilli and/or bifidobacteria. These effects are associated with reduced mucosal inflammation and decreased mucosal lesion scores. Inulin has also been tested in a placebo-controlled clinical trial in patients with relapsing pouchitis. Treatment reduced endoscopic and histological parameters of inflammation of the pouch mucosa. Inulin and oligofructose may offer an opportunity to prevent chronic inflammatory intestinal disorders, and this potential should be tested in further clinical studies.

[xxxi] Watzl, B, et al.  Inulin, oligofructose and immunomodulation. British Journal of Nutrition 93(Suppl. 1):S49-S55 (2005).  Diet is known to modulate immune functions in multiple ways and to affect host resistance to infections. Besides the essential nutrients, non-essential food constituents such as non-digestible carbohydrates may also have an impact on the immune system, especially in the area of the gut-associated lymphoid tissue (GALT). Recent data now provide first evidence that prebiotics such as inulin/oligofructose (IN/OF) modulate functions of the immune system. In animal studies IN/OF primarily activated immune cells in Peyer's patches including IL-10 production and natural killer (NK) cell cytotoxicity. Other immune functions modulated by IN/OF included the concentration of secretory IgA in ileum and caecum, splenic NK cell cytotoxicity as well as splenocyte cytokine production. In different tumor models, a lower incidence of tumors was observed, which in the case of colonic tumors was associated with enhanced NK cell cytotoxicity in the GALT. Few human studies so far have investigated the effects of IN/OF alone or in combination with other dietary supplements on immunocompetence. Supplementation of IN/OF resulted in minor changes of systemic immune functions such as decrease in phagocytic activity. No data are available on the effects of IN/OF on the GALT in man. The mechanisms of the reported effects of IN/OF on the immune system are currently investigated and include: (i) direct effects of lactic acid-producing bacteria or bacterial constituents on immune cells; (ii) the production of SCFA and binding to SCFA receptors on leucocytes. In conclusion, the current data suggest that IN/OF primarily modulate immune parameters in the GALT, but splenocytes are also activated by IN/OF. Human studies are needed to find out whether IN/OF have the potential to modulate systemic immunity in well-nourished individuals and to lower the risk of diseases such as colon cancer.

[xxxii] Delzenne, N, et al.  Prebiotics: actual and potential effects in inflammatory and malignant colonic diseases. Current Opinions in Clinical Nutrition and Metabolic Care 6(5):581-586 (2003).  Animal studies, as well as data obtained in in-vitro cell culture systems, have underlined the potential of certain prebiotics to protect against inflammatory and cancerous processes in the large intestine. Clinical trials are now in progress to assess the relevance of these promising results. The biochemical mechanisms are still incompletely deciphered, but both the promotion of lactic acid-producing bacteria and the production of short-chain fatty acids, particularly butyrate, during the fermentation of prebiotics could be key factors. Enteric resident bacteria are involved in inflammatory bowel diseases and may contribute to colonic carcinogenesis. Dietary manipulation of the flora may thus represent a useful aid to prevent or to treat these diseases, and this could be a place for prebiotics. Inulin-like prebiotics have shown encouraging results in animal models, but clinical and epidemiological trials are necessary to define their efficacy in humans. In the next few years, important advances are expected in understanding the interactions between prebiotics, intestinal flora and the colonic mucosa in health and diseases, enabling the improvement of therapy as well as better nutritional handling of susceptible individuals

[xxxiii] Van Horn, L, et al.  Serum lipid response to a fat-modified, oatmeal-enhanced diet. Preventive Medicine 17(3):377-386 (1988).  236 subjects followed the fat-modified, oatmeal enhanced diet recommended by the American Heart Association for 12 weeks.  By the end of the study, cholesterol levels had dropped significantly, and those who began the study with higher levels of cholesterol experienced the greatest benefit.

[xxxiv] Behall, KM, et al.  Effect of beta-glucan level in oat fiber extracts on blood lipids in men and women. Journal of the American College of Nutrition 16(1):46-51 (1997).  Beta-glucan, a soluble dietary fiber found in oats, significantly reduces overall cholesterol levels in the blood.

[xxxv] Davy, BM, et al.  High-fiber oat cereal compared with wheat cereal consumption favorably alters LDL-cholesterol subclass and particle numbers in middle-aged and older men. American Journal of Clinical Nutrition 76(2):351-358 (2002).  Oat cereal reduced the LDL-cholesterol in the blood of middle-aged and older men compared to wheat cereal.  This may contribute to the cardioprotective effect of oat fiber.

[xxxvi] Weickert, MO, et al.  Cereal fiber improves whole-body insulin sensitivity in overweight and obese women. Diabetes Care 29(4):775-780 (2006).  Increased intake of insoluble dietary fiber increased whole-body insulin sensitivity in overweight and obese women at risk for developing type 2 diabetes.  This may be the mechanism by which fiber decreases the risk of type 2 diabetes.

[xxxvii] Langmead, L, et al.  Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro. Alimentary Pharmacology and Therapeutics 19(5):521-527 (2004).  Aloe vera gel stimulated the release of eicosanoids and IL-8 (anti-inflammatory cytokines) in vitro.  It shows promise in the treatment of inflammatory bowel disease.

[xxxviii] Eamlamnam, K, et al.  Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats. World Journal of Gastroenterology 12(13):2034-2039 (2006).  Aloe vera reduced gastric inflammation, reduces leukocyte adherence and TNF-alpha (an inflammatory cytokine) levels, elevates IL-10 (an anti-inflammatory cytokine), and promote gastric ulcer healing.