Probiotics 3 pp 193-212 | Cite as

Bioactive Peptides from Fermented Foods: Their Role in the Immune System



Fermented foods can be described as products whose physical, chemical and biological characteristics have been modified by the activity of microorganisms. They are known to contain specific microbial metabolites such as alcohol, lactic acid, probionic acid, acetic acid, carbon dioxide and exopolysaccharides, as well as bioprocessed molecules derived from the original food material. These derived products, which could be named “tertiary metabolites”, can play a significant role in the biological activities of fermented products. The fermentation of milk by lactic acid bacteria (LAB) is a good illustration of this phenomenon. We have suggested, about ten years ago (Goulet et al.,1989), that part of the beneficial effect of probiotics might be related to their ability to release bioactive molecules from the substrates on which they are cultivated. Since then, the occurrence of biologically potent molecules derived from the proteolytic attack of milk caseins and whey proteins has been clearly demonstrated and this will be reviewed in this chapter.


Lactic Acid Bacterium Whey Protein Milk Protein Active Peptide Bioactive Peptide 
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  1. Ariyoshi, Y. (1993) Angiotensin-converting enzyme inhibitors derived from food proteins, Trends Food Sci. Tech. 4, 139–144.CrossRefGoogle Scholar
  2. Benjamin, H., Storkson, J., Krewson, J., Sheng, K., Liu, W. and Pariza, M.W. (1991) Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by dietary soy sauce, Cancer Research. 51, 2940–2942.Google Scholar
  3. Bellem, M.A.F., Gibbs, B.F. and Lee, B.H. (1999) Proposing sequences for peptides derived from whey fermentation with potential bioactive sites, J. Dairy Sci. 82, 486–493.CrossRefGoogle Scholar
  4. Berthou, J., Migliore-Samour, D., Lifehitz, A., Delettré, J., Floc’h, F. and Joules, P. (1987) Immunostimulating properties and three-dimensional structure of two tripeptides from human and cow caseins, Fed. Euro. Biochem. Soc. Lett. 218, 55.CrossRefGoogle Scholar
  5. Beucher, S., Levenez, F., Yvon, M. and Coming, T. (1994) Effet du caséinomacropeptide sur la libération de cholecystokinine chez le rat, Reprod Nutr. Dev. 34, 613–614.CrossRefGoogle Scholar
  6. Bounous, G., Papenberg, R., Kongshavn, P.A.L., Gold, P. and Fleiszerzer, D. (1988) Dietary whey protein inhibits the development of dimethylhydrazine induced malignancy, Clin. Invest. Med. 11, 213–217.PubMedGoogle Scholar
  7. Bounous, G., Batist, G. and Gold, P. (1991) Whey proteins in cancer prevention, Cancer Lett. 57, 91–94.PubMedCrossRefGoogle Scholar
  8. Brantl, V., Teschemacher, H., Bläsig, J., Henschen, A. and Lottspeich, F. (1982) Opioid activities of ß-casomorphin, Life Science 28, 1903–1909.CrossRefGoogle Scholar
  9. Chabance, B., Marteau, P., Rambaud, J.C. Migliore-Samour, D., Boynard, M., Pemotin, P., Guillet, R., Jollès, P. and Fiat, A. M. (1998) Casein peptide release and passage to the blood in humans during digestion of milk or yogurt, Biochimie 80, 155–165.PubMedCrossRefGoogle Scholar
  10. Chen, J.R., Suetsuna, K. and Yamauchi, F. (1995) Isolation and characterisation of immunostimulative peptides from soybean, J. Nutr. Biochem. 6, 310–313.CrossRefGoogle Scholar
  11. Costé, M., Rochet, V., Léonil, J., Mollé, D., Bouhallab, S. and Tomé, D. (1992) Identification of C-terminal peptides of bovine I3-casein that enhance proliferation of rat lymphocytes, Immunol. Let. 33, 41–46.CrossRefGoogle Scholar
  12. Cuber, J. C., Bernard, G., Fukiki, T., Bernard, C., Yamanishi, R,, Sugimoto, E. and Chayvialle, J. A. (1990) Luminal CCK-releasing factors in the isolated vasculary perfused rat duodenojejunum, Am. J. Physiol. 259, G191–197.PubMedGoogle Scholar
  13. Demin, A. A., Malinin, V.V. Shataeva, L. K. and Chernova, I. A. (1994) Chromatographic methods for isolation of immunostimulating peptides of milk whey. Appl. Biochem. Microbiol. 30, 255–259.Google Scholar
  14. Desmazeaud, M. (1983) L’état des connaissances en matière de nutrition des bactéries lactiques, Lait 63, 276–274.CrossRefGoogle Scholar
  15. Dziuba, J., Minkiewicz, P., Puszka, K. and Dabrowski, S. (1995) Plant seed storage proteins as potential precursors of bioactive peptides, Polish J Food Nutri. Sci. 4/45, 8, 31–42.Google Scholar
  16. Fujiwara, S., Kadooka, Y, Hirita, T and Nakazato, H. (1990) Screening for mitogenic activity of food microorganisms and their skim milk culture supernatants. J. Jpn. Soc. Nutr. Food Sci. 43, 203.CrossRefGoogle Scholar
  17. Jarizi, M., Migliore-Samour, D., Casabianca-Pignède, M., Kedad, K., Morgat, J. L. Jollés, P. (1992) Specific binding sites on human phagocytic blood cells for Gly-LeuPhe and Val-Glu-Pro-Ile-Pro-Tyr-immunostimulating peptides from human milk proteins, Biochem. Biophys. Acta I 160, 251–261.Google Scholar
  18. Jollès, P., Levy-Toldano, S., Fiat, A.M., Soria, C., Gillessen, D., Thamaidis, A., Dunn, F. W. and Caen, J.P. (1986) Analogy between fibrinogen and casein. Effect of an undecapeptide isolated from 13-casein on platelet function, Euro. J. Biochem. 158, 379–382.CrossRefGoogle Scholar
  19. Hadden, J. W. (1991) Trends Pharmaceut. Sci. 12, 107–111.CrossRefGoogle Scholar
  20. Ganjam, L.S., Thornton, W.H. Marshall, R.T. and Macdonald, R.S. (1997) Antiproliferative effects of yogurt fractions obtained by membrane dialysis on cultured mammalian intestinal cells. J. Dairy Sci, 80, 2325–2329.PubMedCrossRefGoogle Scholar
  21. Gardner, M. (1987) Passage of intact peptides across the intestine, Advances in the Biosciences 65, 99–106.Google Scholar
  22. Gattegno, L., Migliore-Sammour, D, Saffar, L and Jollès, P. (1988) Enhancement of phagocytic activity of human monocytic-macrophagic cells by immunostimulating peptides from human casein. Immunol. Lett. 18, 27.Google Scholar
  23. Goulet, J., Saucier, L. and Moineau, S. (1989) Yoghurt-Nutritional and health properties, Chandan RC (eds ), USA.Google Scholar
  24. Goulet, J. and Matar, C. (1993) Yogurt: myth versus reality conference,Curtis Communication and Research (Ed).Google Scholar
  25. Kayser, H. and Meisel, H. (1996) Stimulation of human peripheral blood lymphocytesby bioactive peptides derived from bovine milk proteins. FEBS letters, 383, 18–20.PubMedCrossRefGoogle Scholar
  26. Keller, R., Keist, R. and Jolla, P. W. (1994) Macrophage response to bacteria and bacterial products: modulation of Fcy receptors and secretory and cellular activities,Immunology 81 161.Google Scholar
  27. Kim, H.D Lee, H.J., Shin, Z.I. Nam, H. S. and Woo, H. J. (1995) Anticancer effects of hydrophobic peptides derived from cheese slurry, Food. Biotech 4 268–272.Google Scholar
  28. Kok, J. (1990). Genetics of the proteolytic system of lactic acid bacteria, FEMS MicrobioL Rev 87,15–24.Google Scholar
  29. Laffineur, E., Genetet, N. and Léonil, J. (1996) Immunodulatory activity of 13-casein permeate medium fermented by lactic acid bacteria, J. Dairy Sci. 79, 2112–2120.PubMedCrossRefGoogle Scholar
  30. Lamn, M., Mazanca, M., Nedrud, J. and Kaetzel, C. (1995) Advances in MucosalImmunology,J. Mestecky et al,(eds), Plenum Press, New York.Google Scholar
  31. Lahov, E. and Regelson, W. (1996) Antibacterial and immunostimulating casein-derived substances from milk: casecidin, isracidin peptides, Food Chem. Toxicol 34 (1), 131–145.PubMedCrossRefGoogle Scholar
  32. MacDonald, R.S., Thornton, W.H. & Marshall, R.T. (1994) A cell culture model to identify biologically active peptides generated by bacterial hydrolysis of casein, J. Dairy Sci 77, 1167–1175.CrossRefGoogle Scholar
  33. Martin-Hernandez, C., Alting, A.C. and Exterkate F.A. (1994) Purification and characterisation of the mature membrane-associated-cell-envelope proteinase of Lactobacillus helveticus L89, Appl. Microbiol. Biotechnol 40, 828–834.CrossRefGoogle Scholar
  34. Maruyama, S., Mitachi, H., Awaja, J., Kurono, M., Tomizaka, N. and Suzuki, H. (1987) Angiotensin 1-converting enzyme inhibitory activity of C-terminal hexapeptide of as1-casein, Agri. Biol. Chem. 51, 2557–2561.CrossRefGoogle Scholar
  35. Matar, C. (1996) Effet de la fermentation du lait par Lactobacillus helveticus sur la liberation de peptides potentiellement bioactifs. Ph. D. thesis. Université Laval, Canada.Google Scholar
  36. Matar, C., Amiot, J., Savoie, L. and Goulet, J. (1996) The effect of milk fermentation by Lactobacillus helveticus on the release of peptides during in vitro digestion, J. Dairy Sci. 79, 971–979.PubMedCrossRefGoogle Scholar
  37. Matar, C. and Goulet, J. (1996) ß-casomorphin-4 from milk fermented by a mutant of Lactobacillus helveticus, Int. Dairy J. 6, 383–397.CrossRefGoogle Scholar
  38. Matar, C., Nadathur, S., Bakalinsky, A. and Goulet, J. (1997) Antimutagenic effects of milk fermented by Lactobacillus helveticus L89 and a protease-deficient derivative, J. Dairy Sci. 80, 1965–70PubMedCrossRefGoogle Scholar
  39. Matsuzaki, T., Hashimoto, S. and Yokokura, T. (1996) effects on antitumor activity and cytokine production in the thoracic cavity by intrapleural administration of Lactobacillus casei in tumor-bearing mice, Med. Microbiol. Immunol. 185: 157–161.PubMedCrossRefGoogle Scholar
  40. McIntosh, G.H., Regester, G.O., Leu, R.K.L., Royle, P.J. and Smithers, G.W. (1995) Dairy products protect against dimethylhydrazine-induced intestinal cancer in rats. J. Nutr. 125, 809–816.PubMedGoogle Scholar
  41. Meisel, H., Frister, H. and Schlimme, E. (1989) Biologically active peptides in milk proteins, Z. Ernahrungswiss 28, 267–278.PubMedCrossRefGoogle Scholar
  42. Meisel, H. (1993) New Perspectives in Infant Nutrition. G. Sawazki and B. Renner, Stuttgart.Google Scholar
  43. Meisel, H. and Schlimme, E. (1994) 13-Casomorphins and Related Peptides: recent developments, Brantl, V. and Teschemacher, H. (eds ), VCH-Weinhein.Google Scholar
  44. Migliore-Samour, D., Floc’h, F. and Jollès, P. (1989) Biologically active peptides implicated in immunodulation, J. Dairy Res. 56: 3–57.CrossRefGoogle Scholar
  45. Miyauchi, H., Kaino, A., Schinoda, I., Fukuwatari, Y. and Hayasawa, H. (1997) Immunodulating effect of bovine lactoferrin pepsin hydrolysate on murine splenocytes and Peyer’s patch cells. J. Dairy Sci 80, 2330–2339.PubMedCrossRefGoogle Scholar
  46. Moineau, S. and Goulet, J. (1991) Effect of feeding fermented milks on the pulmonary macrophage activity in mice, Milchwissenschaft 46, 551–554.Google Scholar
  47. Mokotoff, M., Zhao, H., Roth, S.M., Shelly, J.A., Slavoski, J.N. and Koutlab, N.M. (1990) Thymosin like peptides as potential immunostimulants. Synthesis via the polymeric reagent method, J. Med Chem 33, 354–360.PubMedCrossRefGoogle Scholar
  48. Morelli, L., Vesco, M. Coaonelli, P. S. and Botazi, V. (1986) Fast and slow milk coagulating variants of Lactobacillus helveticus HLM1. Can J Microbiol. 32, 758.PubMedCrossRefGoogle Scholar
  49. Mullally, M., Meisel, M. and Fitzgerald, R. (1997) Angiotensin-I-converting enzyme inhibitory activities of gastric and pancreatic proteinase digests of whey proteins, Int. Dairy J. 7, 299–303.CrossRefGoogle Scholar
  50. Nakamura, Y., Yamamoto, N., Kakai, A., Okubo, S., Yamazaki, S. and Takano, T. (1995) Purification and characterisation of angiotensin I-converting enzyme inhibitors from sour milk, J. Dairy Sci 78, 777–781PubMedCrossRefGoogle Scholar
  51. Nardi, M., Chopin, M.C., Chopin, A., Cals, M.M. and Gripon, J.C. (1991) Cloning and DNA sequence analysis of X-prolyl-dipeptidyl aminopeptidse from Lactococcus lactis subsp. lactis NCD0763, Appt Environ. Microbiol 57, 45–50.Google Scholar
  52. Ole-Moi Yoi, O. K. and Brown, W. C. (1993) Evidence for the induction of casein kinase II in bovine lymphocytes transformed by the intracellular protozoan parasite Theileria parva. EMBA J. 12, 1621–1631.Google Scholar
  53. Otani, H. and Monnai, M. (1993) Inhibition of proliferative responses of mouse spleen lymphocytes by bovine ic-casein digests, Food Agri. Immunol 5, 219–229.CrossRefGoogle Scholar
  54. Parker, F., Migliore-Samour, D., Floc’h, F., Zerial, A., Werner, G. H. Jollès, J., Casaretto, M., Zahn, H. and Jollès, P. (1984) Immunostimulating hexapeptide from human casein: amino acid sequence, synthesis and biological properties. Euro. J. Biochem 145, 677–682.Google Scholar
  55. Perdigon, G., De Jorrat, M. E., De Petrino, S. F. & Rachid, M. (1993) Antitumor activity of orally administered Lactobacillus casei: significance of its dose in the inhibition of a fibrosarcoma in mice, Food Agri. Immun. 5, 39–49.CrossRefGoogle Scholar
  56. Perdigon, G., Alvarez, S., Medici, M., Vintini, E., De Giori, G., De Kairuz, M. and Holgado de Ruiz, A. P. (1995) Effect of yogurt with different storage period on the immune system in mice, Milchwissenschaft 50 (7), 367–371.Google Scholar
  57. Perdigon, G., Valdez, J. C. and Rachid, M. (1998) Antitumor activity of yogurt: study of possible immune mechanisms, J. Dairy Res. 65, 129–138.PubMedCrossRefGoogle Scholar
  58. Prasad, C., Kumar, S., Adkinson, W and McGregor, J. (1995) Hormones in foods: abundance of authentic cyclo(His-Pro)-like immunoreactivity in milk and yogurt, Nutr. Res. 15, 1623–1635.CrossRefGoogle Scholar
  59. Prichard, G.G. and Goolbear, T. (1993) The physiology and biochemistry of the proteolytic system in lactic acid bacteria, FEMS Microbiol. Rev 12, 179–206.CrossRefGoogle Scholar
  60. Seki, E., Katsuhiro, 0., Matsufuji, H., Matsui, T. and Osajima, Y. (1995) Nippon Nögeikagaku Kaishi, 69, 1171–1174.Google Scholar
  61. Suetsuna, K., Chen, J.R. and Yamauchi, F. (1991) Immunostimulating peptides derived from sardine muscle and soybean protein; amino acid sequence, synthesis and biological properties, Clin. Rep. 25 (15), 75–86.Google Scholar
  62. Sütas, Y., Soppi, E., Korhonen, H., Syvdoja, E.L., Saxelin, M. and Rokka, T. (1996a) Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolysed with Lactobacillus casei GG-derived enzymes, J. Allergy Clin. Immunol. 98, 216–224.PubMedCrossRefGoogle Scholar
  63. Sütas, Y., Hume, M. and Isolauri, E. (1996b) Downregulation of anti CD3 antibody-induced II-4 production by bovine caseins hydrolysed with Lactobacillus GG-derived enzymes, Scand. J. Immunol. 43, 687–689.PubMedCrossRefGoogle Scholar
  64. Takahashi, M., Moriguchi., S., Ikeno, M., Kono, S., Ohata, K., Usui, H., Kurahashi, K., Sasaki, R. and Yoshikawa, M. (1996) Studies on the ileum-contracting mechanisms and identification as a complement C3a receptor agonist of oryzatensin, a bioactive peptide derived from rice albumin, Peptides 17, 5–12Google Scholar
  65. Tamang, J. P. (1998) Role of microorganisms in traditional fermented foods, Indian Food Industry, 17 (3), 162–167.Google Scholar
  66. Tan, P.S., Van Kessel, T A., Veerdonk, F.M. Zurendock, P.F. Buins, A.P. and Konnings, W.N. (1993) Degradation and debittering of a tryptic digest from (3-casein by arninopeptidase N from Lactococcus lactis subsp. cremoris WG2. Appl. Environ. Microbiol. 59, 1430–1436.Google Scholar
  67. Tomioka, H. and Saito, R. (1992) Lactic Acid Bacteria, Elsevier Applied Science, London.Google Scholar
  68. Van Boekel, M.A J.S., Weerens, C.N.J.M., Holstra, A., Scheidtweiler, C.E. and Alink, G.M. (1993) Antimutagenic effects of casein and its digestion products, Food Chem. Toxicol. 31 (10), 731–737.PubMedCrossRefGoogle Scholar
  69. Valdez, J. C., Rachid, M., Bru, E. and Perdigon, G. (1997) The effect of yoghurt on the cytotoxic and phagocytic activity of macrophages in tumor-bearing mice, Food. Agri. Immunol. 9, 299–308.CrossRefGoogle Scholar
  70. Vis, E., Plinck, A., Alink, G. and Van Boekel, M.A.J.S. (1998) Antimutagenicity of heat-denatured ovalbumin, before and after digestion as compared to caseinate, BSA, and soy proteins, J. Agric. Food. Chem. 46, 3713–3718.CrossRefGoogle Scholar
  71. Visser, S., Exterkate, F.A., Slangen, C.J. and de Veer, G.J.C.M. (1986) Comparative study of action of cell wall proteinases from various strains of Streptococcus cremoris on bovine (a,1 -, 13- and x-casein, Appl. Environ. Microbiol. 52, 1162–1166.PubMedGoogle Scholar
  72. Visser, S. (1993) Proteolytic enzymes and their relation to cheese ripening and flavor: an overview. J. Dairy Sci. 76, 329–350.CrossRefGoogle Scholar
  73. Watanabe, H., Takahashi, T., Ishimoto, T. and Ito, A. (1991) The effect of miso diet on small intestinal damage in mice irradiated by X-ray. Sci. Technol. Miso. 39, 29–32.Google Scholar
  74. Yamamoto, N., Akino, A. and Takano, T. (1994) Antihypertensive effects of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790, J. Dairy Sci. 77, 917–922.PubMedCrossRefGoogle Scholar
  75. Yvon, M., Beucher, S., Guilloteau, P., Le Hueron-Luron, I. and Corring, T. (1994) Effects of caseinomacropeptide (CMP) on digestion regulation, Reprod, Nutr. Dev. 34, 527–537.CrossRefGoogle Scholar
  76. Yoo, Y.C., Watanabe, S., Watanabe, R., Hata, K., Shimazaki, K. and Azuma, I. (1997). Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice, Jpn. J. Cancer Res. 88, 189–190.CrossRefGoogle Scholar
  77. Zevaco, C. and Gripon, J.C. (1988) Properties and specificity of the cell-wall proteinase from Lactobacillus helveticus, Lait 68, 393–408.CrossRefGoogle Scholar

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