Молозиво крупного рогатого скота в профилактике инфекционных заболеваний человека (обзор литературы)

Молозиво (или иммунное молоко) — первое молоко, которое вырабатывают млекопитающие после родов, и его состав заметно отличается от молока, получаемого позже в период лактации. Молозиво является богатым источником иммуноглобулинов и других биологически активных компонентов. 

Цель данного обзора литературы — систематизация исследований о способах лечения и профилактики инфекционных заболеваний человека с использованием иммуномодулирующих и иммунопротекторных свойств молозива. Изучены открытые источники, размещённые в базах данных PubMed, ResearherGate и eLibrary.

История применения молозива гипериммунизированных коров в качестве средства лечения заболеваний человека прослеживается до 1950-х гг. Полученные данные свидетельствуют о высокой эффективности применения молозива коров и его компонентов как для профилактики, так и для лечения инфекционных заболеваний. Молозиво способно производить гетерологический перенос пассивного иммунитета. Протоколы иммунизации, применяемые при производстве иммунного молока, могут быть сильно вариабельны. В особенности это касается сроков иммунизации. Работа по протоколам иммунизации, при которых животные подвергаются воздействиям конкретных антигенов, в результате может усилить гуморальные иммунные ответы в молочной железе. 

Наиболее актуален поиск путей применения иммунного молока в качестве средства для сдерживания пандемии SARS-CoV-2. В обзоре литературы приведена характеристика противомикробных, иммуномодулирующих и стимулирующих рост факторов в молозиве крупного рогатого скота. Приведены примеры и описание гомологической и гетерологической передачи пассивного иммунитета. 

Участие авторов:

Кузьмин С.В., Майзель С.Г., Алешкин В.А. — концепция и дизайн исследования;

Скрипачева А.И. — написание текста, составление списка литературы;

Русаков В.Н. — концепция исследования, написание текста; 

Синицына О.О. — концепция и дизайн исследования, редактирование.

Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Финансирование. Исследование не имело спонсорской поддержки. 

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Поступила 10.01.2022

Принята в печать 11.03.2022

Опубликована 04.05.2022

1. Кокряков В.Н. Очерки о врожденном иммунитете. СПб.: Наука; 2006.

2. Федоров Ю.Н., Клюквина В.И., Богомолова О.А., Романенко М.Н. Колостральный иммунитет и иммунопрофилактика болезней новорожденных телят. Ветеринария. 2016; (5): 3-7.

3. Сергеев В.А., Непоклонов Е.А., Алипер Т.И. Вирусы и вирусные вакцины. М.: Библионика; 2007.

4. Хаитов Р.М., Игнатьев Г.А., Сидорович И.Г. Иммунология. Норма и патология. М.: Медицина; 2010.

5. Корякина Л.П. Особенности клеточного состава молозива коров в первые сутки лактации. Достижение науки и техники АПК. 2011; (2): 54-5.

6. Малашко В.В., Кузнецов Н.А. Иммуноглобулины молозива. Гродно; 2010.

7. Скопичев В.Г., Яковлев В.Г. Частная физиология. Часть 2. Физиология продуктивных животных. М.: Колос; 2008.

8. Bjornvad C.R., Thymann T., Deutz N.E., et al. Enteral feeding induces diet-dependent mucosal dysfunction, bacterial proliferation, and necrotizing enterocolitis in preterm pigs on parenteral nutrition. Am. J. Physiol. Gastrointest. Liver Physiol. 2008; 295(5): G1092-103. https://doi.org/10.1152/ajpgi.00414.2007

9. Campbell B., Petersen W.E. Immune milk-A historical survey. Dairy Sci. Abstr. 1963; 25, 345-58.

10. Lascelles A.K. A review of the literature on some aspects of immune milk. Dairy Sci. Abstr. 1963; 25: 359-64.

11. Alisky J. Bovine and human-derived passive immunization could help slow a future avian influenza pandemic. Med. Hypotheses. 2009; 72(1): 74-5. https://doi.org/10.1016/j.mehy.2008.08.016

12. Yolken R.H., Losonsky G.A., Vonderfecht S., Leister F., Wee S.B. Antibody to human rotavirus in cow’s milk. N. Engl. J. Med. 1985; 312(10): 605-10. https://doi.org/10.1056/nejm198503073121002

13. Li-Chan E., Kummer A., Losso J.N., Nakai S. Survey of immunoglobulin G content and antibody specificity in cow’s milk from British Columbia. Food Agric. Immunol. 1994; 6(4): 443-51.

14. Stelwagen K., Carpenter E., Haigh B., Hodgkinson A., Wheeler T.T. Immune components of bovine colostrum and milk. J. Anim. Sci. 2009; 87(13 Suppl.): 3-9. https://doi.org/10.2527/jas.2008-1377

15. Hurley W.L., Theil P.K. Perspectives on immunoglobulins in colostrum and milk. Nutrients. 2011; 3(4): 442-74. https://doi.org/10.3390/nu3040442

16. Pakkanen R., Aalto J. Growth factors and antimicrobial factors of bovine colostrum.Int. Dairy J. 1997; 7(5): 285-97.

17. Izumi H., Kosaka N., Shimizu T., Sekine K., Ochiya T., Takase M. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions. J. Dairy Sci. 2012; 95(9): 4831-41. https://doi.org/10.3168/jds.2012-5489

18. Hata T., Murakami K., Nakatani H., Yamamoto Y., Matsuda T., Aoki N. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs. Biochem. Biophys. Res.Commun. 2010; 396(2): 528-33. https://doi.org/10.1016/j.bbrc.2010.04.135

19. Sun Q., Chen X., Yu J., Zen K., Zhang C.Y., Li L. Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum. Protein Cell. 2013; 4(3): 197-210. https://doi.org/10.1007/s13238-013-2119-9

20. Gopal P.K., Gill H.S. Oligosaccharides and glycoconjugates in bovine milk and colostrum. Br. J. Nutr. 2000; 84(Suppl. 1): S69-S74. https://doi.org/10.1017/s0007114500002270

21. Purup S., Vestergaard M., Pedersen O., Sejrsen K. Biological activity of bovine milk on proliferation of human intestinal cells. J. Dairy Res. 2007; 74(1): 58-65. https://doi.org/10.1017/s0022029906002093

22. Playford R.J., MacDonald C.E., Johnson W.S. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. Am. J. Clin. Nutr. 2000; 72(1): 5-14. https://doi.org/10.1093/ajcn/72.1.5

23. Sacerdote P., Mussano F., Franchi S., Panerai A.E., Bussolati G., Carossa S., et al. Biological components in a standardized derivative of bovine colostrum. J. Dairy Sci. 2013; 96(3): 1745-54. https://doi.org/10.3168/jds.2012-5928

24. Elfstrand L., Lindmark-Månsson H., Paulsson M., Nyberg L., Åkesson B. Immunoglobulins, growth factors and growth hormone in bovine colostrum and the effects of processing.Int. Dairy J. 2002; 12(11): 879-87.

25. Roos N., Mahe S., Benamouzig R., Sick H., Rautureau J., Tomé D. 15N-labeled immunoglobulins from bovine colostrum are partially resistant to digestion in human intestine. J. Nutr. 1995; 125(5): 1238-44. https://doi.org/10.1093/jn/125.5.1238

26. Kelly C.P., Chetham S., Keates S., Bostwick E.F., Roush A.M., Castagliuolo I., et al. Survival of anti-Clostridium difficile bovine immunoglobulin concentrate in the human gastrointestinal tract. Antimicrob. Agents Chemother. 1997; 41(2): 236-41. https://doi.org/10.1128/aac.41.2.236

27. Lilius E.M., Marnila P. The role of colostral antibodies in prevention of microbial infections. Curr. Opin. Infect. Dis. 2001; 14(3): 295-300. https://doi.org/10.1097/00001432-200106000-00008

28. Glass R.I., Svennerholm A.M., Stoll B.J., Khan M.R., Hossain K.M.B., Huq M.I., et al. Protection against cholera in breast-fed children by antibodies in breast milk. N. Engl. J. Med. 1983; 398(23): 1389-92. https://doi.org/10.1056/nejm198306093082304

29. Ruiz-Palacios G.M., Calva J.J., Pickering L.K., Lopez-Vidal Y., Volkow P., Pezzarossi H., et al. Protection of breast-fed infants against Campylobacter diarrhea by antibodies in human milk. J. Pediatr. 1990; 116(5): 707-13. https://doi.org/10.1016/s0022-3476(05)82652-6

30. Moon H.W., Bunn T.O. Vaccines for preventing enterotoxigenic Escherichia coli infections in farm animals. Vaccine. 1993; 11(2): 213-20. https://doi.org/10.1016/0264-410x(93)90020-x

31. Saif L.J., Smith K.L., Landmeier B.J., Bohl E.H., Theil K.W., Todhunter D.A. Immune response of pregnant cows to bovine rotavirus immunization. Am. J. Vet. Res. 1984; 45(1): 49-58.

32. Lanza I., Shoup D.I., Saif L.J. Lactogenic immunity and milk antibody isotypes to transmissible gastroenteritis virus in sows exposed to porcine respiratory coronavirus during pregnancy. Am. J. Vet. Res. 1995; 56(6): 739-48.

33. Wilson M.R., Brown P., Svendsen J. Immunity to Escherichia coli in pigs: Antibody secretion by the mammary gland after intramammary or intramuscular vaccination with E. coli vaccine. Can. J.Comp. Med. 1972; 36(1): 44-8.

34. Kortbeek-Jacobs J.M.C., van Kooten P.J.S., van der Donk J.A., van Dijk J.E., Rutten V.P. The effect of oral immunization on the population of lymphocytes migrating to the mammary gland of the sow. Vet. Microbiol. 1984; 9(3): 287-99. https://doi.org/10.1016/0378-1135(84)90046-4

35. Parreño V., Béjar C., Vagnozzi A., Barrandeguy M., Costantini V., Craig M.I., et al. Modulation by colostrum-acquired maternal antibodies of systemic and mucosal antibody responses to rotavirus in calves experimentally challenged with bovine rotavirus. Vet. Immunol. Immunopathol. 2004; 100(1-2): 7-24. https://doi.org/10.1016/j.vetimm.2004.02.007

36. Snodgrass D.R., Campbell I., Mwenda J.M., Chege G., Suleman M.A., Morein B., et al. Stimulation of rotavirus IgA, IgG and neutralizing antibodies in baboon milk by parenteral vaccination. Vaccine. 1995; 13(4): 408-13. https://doi.org/10.1016/0264-410x(95)98265-c

37. Shahid N.S., Steinhoff M.C., Roy E., Begum T., Thompson C.M., Siber G.R. Placental and breast transfer of antibodies after maternal immunization with polysaccharide meningococcal vaccine: а randomized, controlled evaluation. Vaccine. 2002; 20(17-18): 2404-9. https://doi.org/10.1016/s0264-410x(02)00061-0

38. Butler J.E., Kehrli M.E. Jr. Immunoglobulins and immunocytes in the mammary gland and its secretions. In: Mestecky J., Lamm M., Strober W., Bienenstock J., McGhee J.R., Mayer L., eds. Mucosal Immunology. Burlington, MA: Elsevier Academic Press; 2005.

39. Schaller J.P., Saif L.J., Cordle C.T., Candler E. Jr., Winship T.R., Smith K.L. Prevention of human rotavirus-induced diarrhea in gnotobiotic piglets using bovine antibody. J. Infect. Dis. 1992; 165(4): 623-30. https://doi.org/10.1093/infdis/165.4.623

40. Jenkins M.C., O’Brien C., Trout J., Guidry A., Fayer R. Hyperimmune bovine colostrum specific for recombinant Cryptosporidium parvum antigen confers partial protection against cryptosporidiosis in immunosuppressed adult mice. Vaccine. 1999; 17(19): 2453-60. https://doi.org/10.1016/s0264-410x(98)00369-7

41. Huang X.H., Chen L., Gao W., Zhang W., Chen S.J., Xu L.B., et al. Specific IgG activity of bovine immune milk against diarrhea bacteria and its protective effects on pathogen-infected intestinal damages. Vaccine. 2008; 26(47): 5973-80. https://doi.org/10.1016/j.vaccine.2008.08.040

42. Ebina T., Sato A., Umezu K., Ishida N., Ohyama S., Oizumi A., et al. Prevention of rotavirus infection by cow colostrum containing antibody against human rotavirus. Lancet. 1983; 322(8357): 1029-30. https://doi.org/10.1016/S0140-6736(83)91016-4

43. Ebina T., Sato A., Umezu K., Ishida N., Ohyama S., Oizumi A., et al. Prevention of rotavirus infection by oral administration of cow colostrum containing antihumanrotavirus antibody. Med. Microbiol. Immunol. 1985; 174(4): 177-85. https://doi.org/10.1007/bf02123694

44. Hilpert H., Brussow H., Mietens C., Sidoti J., Lerner L., Werchau H. Use of bovine milk concentrate containing antibody to rotavirus to treat rotavirus gastroenteritis in infants. J. Infect. Dis. 1987; 156(1): 158-66. https://doi.org/10.1093/infdis/156.1.158

45. Mitra A.K., Mahalanabis D., Ashraf H., Unicomb L., Eeckels R., Tzipori S. Hyperimmune cow colostrum reduces diarrhoea due to rotavirus: A double-blind, controlled clinical trial. Acta Paediatr. 1995; 84(9): 996-1001. https://doi.org/10.1111/j.1651-2227.1995.tb13814.x

46. Davidson G.P., Whyte P.B.D., Daniels E., Franklin K., Nunan H., McCloud P.I., et al. Passive immunization of children with bovine colostrum containing antibodies to human rotavirus. Lancet. 1989; 2(8665): 709-12. https://doi.org/10.1016/s0140-6736(89)90771-x

47. Civra A., Altomare A., Francese R., Donalisio M., Aldini G., Lembo D. Colostrum from cows immunized with a veterinary vaccine against bovine rotavirus displays enhanced in vitro anti-human rotavirus activity. J. Dairy Sci. 2019; 102(6): 4857-69. https://doi.org/10.3168/jds.2018-16016

48. Ng W.C., Wong V., Muller B., Rawlin G., Brown L.E. Prevention and treatment of influenza with hyperimmune bovine colostrum antibody. PLoS One. 2010; 5(10): e13622. https://doi.org/10.1371/journal.pone.0013622

49. Huppertz H.I., Rutkowski S., Busch D., Eisebit R., Lissner R., Karch H. Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, Shiga toxin-producing E. coli, and E. coli expressing intimin and hemolysin. J. Pediatr. Gastroenterol. Nutr. 1999; 29(4): 452-6. https://doi.org/10.1097/00005176-199910000-00015

50. Struff W.G., Sprotte G. Bovine colostrum as a biologic in clinical medicine; a review. Part I: Biotechnological standards, pharmacodynamic and pharmacokinetic characteristics and principles of treatment.Int. J. Clin. Pharmacol. Ther. 2007; 45(4): 193-202. https://doi.org/10.5414/cpp45193

51. Struff W.G., Sprotte G. Bovine colostrum as a biologic in clinical medicine; a review-Part II: Clinical studies.Int. J. Clin. Pharmacol. Ther. 2008; 46(5): 211-25. https://doi.org/10.5414/cpp46211

52. Stephan W., Dichtelmuller H., Lissner R. Antibodies from colostrum in oral immunotherapy. J. Clin. Chem. Clin. Biochem. 1990; 28(1): 19-23.

53. Ashraf H., Mahalanabis D., Mitra A.K., Tzipori S., Fuchs G.J. Hyperimmune bovine colostrum in the treatment of shigellosis in children: A double-blind, randomized, controlled trial. Acta Paediatr. 2001; 90(12): 1373-8. https://doi.org/10.1080/08035250152708743

54. Brinkworth G., Buckley J. Concentrated bovine colostrum protein supplementation reduces the incidence of self-reported symptoms of upper respiratory tract infection in adult males. Eur. J. Nutr. 2003; 42(4): 228-32. https://doi.org/10.1007/s00394-003-0410-x

55. Shing C.M., Peake J., Suzuki K., Okutsu M., Pereira R., Stevenson L., et al. Effects of bovine colostrum supplementation on immune variables in highly trained cyclists. J. Appl. Physiol. (1985). 2007; 102(3): 1113-22. https://doi.org/10.1152/japplphysiol.00553.2006

56. Crooks C.V., Wall C.R., Cross M.L., Rutherfurd-Markwick K.J. The effect of bovine colostrum supplementation on salivary IgA in distance runners.Int. J. Sport. Nutr. Exerc. Metab. 2006; 16(1): 47-64. https://doi.org/10.1123/ijsnem.16.1.47

57. Crooks C.V., Wall C.R., Cross M.L., Rutherfurd-Markwick K.J. Effect of bovine colostrum supplementation on respiratory tract mucosal defenses in swimmers.Int. J. Sport. Nutr. Exerc. Metab. 2010; 20(3): 224-35. https://doi.org/10.1123/ijsnem.20.3.224

58. Patiroglu T., Kondolot M. The effect of bovine colostrum on viral upper respiratory tract infections in children with immunoglobulin A deficiency. Clin. Respir. J. 2013; 7(1): 21-6. https://doi.org/10.1111/j.1752-699X.2011.00268.x

59. Huppertz H.I., Rutkowski S., Busch D.H., Eisebit R., Lissner R., Karch H. Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, shiga toxin-producing E. coli, and E. coli expressing intimin and hemolysin. J. Pediatr. Gastroenterol. Nutr. 1999; 29(4): 452-6. https://doi.org/10.1097/00005176-199910000-00015

60. He F., Tuomola E., Arvilommi H., Salminen S. Modulation of human humoral immune response through orally administered bovine colostrum. FEMS Immunol. Med. Microbiol. 2001; 31(2): 93-6. https://doi.org/10.1111/j.1574-695x.2001.tb00504.x

61. Wolvers D.A., van Herpen-Broekmans W.M., Logman M.H., van der Wielen R.P., Albers R. Effect of a mixture of micronutrients, but not of bovine colostrum concentrate, on immune function parameters in healthy volunteers: a randomized placebo-controlled study. Nutr. J. 2006; 5: 28. https://doi.org/10.1186/1475-2891-5-28

62. Mikic I.M., Davidovic B.L., Matijevic J., Prpić Mehičić G., Jukić Krmek S. A pilot study of effects of ecolostrum on salivary IgA. Acta Stomatol. Croat. 2012; 46(2): 111-6.

63. Jensen G.S., Patel D., Benson K.F. A novel extract from bovine colostrum whey supports innate immune functions. II. Rapid changes in cellular immune function in humans. Prev. Med. 2012; 54(Suppl.): S124-9. https://doi.org/10.1016/j.ypmed.2012.01.004

64. Appukutty M., Radhakrishnan A.K., Ramasamy K., Bakar A., Majeed A., Noor M.I., et al. Modulation of interferon gamma response through orally administered bovine colostrum in active adolescent boys. Biomed. Res. 2011; 22(1): 18-22.

65. Mietens C., Keinhorst H., Hilpert H., Gerber H., Amster H., Pahud J.J. Treatment of infantile E. coli gastroenteritis with specific bovine anti-E. coli milk immunoglobulins. Eur. J. Pediatr. 1979; 132(4): 239-52. https://doi.org/10.1007/bf00496847

66. Tacket C.O., Losonsky G., Link H., Hoang Y., Guesry P., Hilpert H., et al. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. N. Engl. J. Med. 1988; 318(19): 1240-3. https://doi.org/10.1056/nejm198805123181904

67. Loimaranta V., Carlén A., Olsson J., Tenovuo J., Syvaoja E.L., Korhonen H. Concentrated bovine colostral whey proteins from Streptococcus mutans/Strep. sorbinus immunized cows inhibit the adherence of Strep. mutans and promote the aggregation of mutans streptococci. J. Dairy Res. 1998; 65(4): 599-607. https://doi.org/10.1017/s0022029998003069

68. Loimaranta V., Tenovuo J., Virtanen S., Marnila P., Syvaoja E.L., Tupasela T., et al. Generation of bovine immune colostrum against Streptococcus mutans and Streptococcus sobrinus and its effect on glucose uptake and extracellular polysaccharide formation by mutans streptococci. Vaccine. 1997; 15(11): 1261-8. https://doi.org/10.1016/s0264-410x(97)00027-3

69. Oho T., Shimazaki Y., Mitoma M., Yoshimura M., Yamashita Y., Okano K., et al. Bovine milk antibodies against cell surface protein antigen PAc-glucosyltransferase fusion protein suppress cell adhesion and alter glucan synthesis of Streptococcus mutans. J. Nutr. 1999; 129(10): 1836-41. https://doi.org/10.1093/jn/129.10.1836

70. Tzipori S., Roberton D., Chapman C. Remission of diarrhoea due to cryptosporidiosis in an immunodeficient child treated with hyperimmune bovine colostrum. Br. Med. J. (Clin. Res. Ed.) 1986; 293(6557): 1276-7. https://doi.org/10.1136/bmj.293.6557.1276

71. Kelly C.P., Pothoulakis C., Vavva F., Castagliuolo I., Bostwick E.F., O’Keane J.C., et al. Anti-Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotoxicity of C. difficile toxins. Antimicrob. Agents Chemother. 1996; 40(2): 373-9. https://doi.org/10.1128/aac.40.2.373

72. Hodgkinson A.J., Cannon R.D., Holmes A.R., Fischer F.J., Willix-Payne D.J. Production from dairy cows of semi-industrial quantities of milk-protein concentrate (MPC) containing efficacious anti-Candida albicans IgA antibodies. J. Dairy Res. 2007; 74(3): 269-75. https://doi.org/10.1017/s0022029907002567

73. Shkreta L., Talbot B.G., Diarra M.S., Lacasse P. Immune responses to a DNA/protein vaccination strategy against Staphylococcus aureus induced mastitis in dairy cows. Vaccine. 2004; 23(1): 114-26. https://doi.org/10.1016/j.vaccine.2004.05.002

74. Castagliuolo I., Piccinini R., Beggiao E., Palu G., Mengoli C., Ditadi F., et al. Mucosal genetic immunization against four adhesions protects against Staphylococcus aureus-induced mastitis in mice. Vaccine. 2006; 24(20): 4393-402. https://doi.org/10.1016/j.vaccine.2006.02.055

75. Dorosko S.M., Ayres S.L., Connor R.L. Induction of HIV-1 MPR(649-684)-specific IgA and IgG antibodies in caprine colostrum using a peptide-based vaccine. Vaccine. 2008; 26(42): 5416-22. https://doi.org/10.1016/j.vaccine.2008.07.079

76. O’Brien C.N., Guidry A.J., Douglass L.W., Westhoff D.C. Immunization with Staphylococcus aureus lysate incorporated into microspheres. J. Dairy Sci. 2001; 84(8): 1791-9. https://doi.org/10.3168/jds.s0022-0302(01)74617-6

77. Liu G.L., Wang J.Q., Bu D.P., Cheng J.B., Zhang C.G., Wei H.Y., et al. Specific immune milk production of cows implanted with antigen-release devices. J. Dairy Sci. 2009; 92(1): 100-8. https://doi.org/10.3168/jds.2008-1114

78. Toledo J.R., Sanchez O., Montesino R., Farnos O., Rodriguez M.P., Alfonso P., et al. Highly protective E2-CSFV vaccine candidate produced in the mammary gland of adenoviral transduced goats. J. Biotechnol. 2008; 133(3): 370-6. https://doi.org/10.1016/j.jbiotec.2007.09.014

79. Rump J.A., Arndt R., Arnold A., Bendick C., Dichtelmüller H., Franke M., et al. Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum. Clin. Investig. 1992; 70(7): 588-94. https://doi.org/10.1007/bf00184800

80. Plettenberg A., Stoehr A., Stellbrink H.J., Albrecht H., Meigel W. A preparation from bovine colostrum in the treatment of HIV-positive patients with chronic diarrhea. Clin. Investig. 1993; 71(1): 42-5. https://doi.org/10.1007/bf00210962

81. Lund P., Sangild P.T., Aunsholt L., Hartmann B., Holst J.J., Mortensen J., et al. Randomised controlled trial of colostrum to improve intestinal function in patients with short bowel syndrome. Eur. J. Clin. Nutr. 2012; 66(9): 1059-65. https://doi.org/10.1038/ejcn.2012.93

82. Kerksick C.M., Rasmussen C., Lancaster S., Starks M., Smith P., Melton C., et al. Impact of differing protein sources and a creatine containing nutritional formula after 12 weeks of resistance training. Nutrition. 2007; 23(9): 647-56. https://doi.org/10.1016/j.nut.2007.06.015

83. Playford R.J., MacDonald C.E., Calnan D.P., Floyd D.N., Podas T., Johnson W., 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(6): 627-33.

84. Florén C.H., Chinenye S., Elfstrand L., Hagman C., Ihse I. ColoPlus, a new product based on bovine colostrum, alleviates HIV-associated diarrhoea. Scand. J. Gastroenterol. 2006; 41(6): 682-6. https://doi.org/10.1080/00365520500380817

85. Bolke E., Jehle P.M., Hausmann F., Däubler A., Wiedeck H., Steinbach G., et al. Preoperative oral application of immunoglobulin-enriched colostrum milk and mediator response during abdominal surgery. Shock. 2002; 17(1): 9-12. https://doi.org/10.1097/00024382-200201000-00002

86. Panahi Y., Falahi G., Falahpour M., Moharamzad Y., Khorasgani M.R., Beiraghdar F., et al. Bovine colostrum in the management of nonorganic failure to thrive: a randomized clinical trial. J. Pediatr. Gastroenterol. Nutr. 2010; 50(5): 551-4. https://doi.org/10.1097/mpg.0b013e3181b91307

87. Buckley J.D., Butler R.N., Southcott E., Brinkworth G.D. Bovine colostrum supplementation during running training increases intestinal permeability. Nutrients. 2009; 1(2): 224-34. https://doi.org/10.3390/nu1020224

88. Hofman Z., Smeets R., Verlaan G., Lugt Rv., Verstappen P.A. The effect of bovine colostrum supplementation on exercise performance in elite field hockey players.Int. J. Sport Nutr. Exerc. Metab. 2002; 12(4): 461-9. https://doi.org/10.1123/ijsnem.12.4.461

89. Davis P.F., Greenhill N.S., Rowan A.M., Schollum L.M. The safety of New Zealand bovine colostrum: nutritional and physiological evaluation in rats. Food Chem. Toxicol. 2007; 45(2): 229-36. https://doi.org/10.1016/j.fct.2006.07.034

90. Kaducu F.O., Okia S.A., Upenytho G., Elfstrand L., Florén C.H. Effect of bovine colostrum-based food supplement in the treatment of HIV-associated diarrhea in Northern Uganda: a randomized controlled trial. Indian J. Gastroenterol. 2011; 30(6): 270-6. https://doi.org/10.1007/s12664-011-0146-0