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Gut. Feb 1999; 44(2): 212–217.
PMCID: PMC1727384

Bovine immunoglobulin concentrate-Clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine

Abstract

Background—Bovine immunoglobulin concentrate (BIC)-Clostridium difficile is prepared from the colostrum of cows immunised against C difficile toxins and contains high concentrations of neutralising IgG antitoxin.
Aims—To determine the proportion of BIC-C difficile which survives passage through the human stomach and small intestine.
Methods—Six volunteers with an end ileostomy took 5 g of BIC-C difficile containing 2.1 g of bovine IgG on four occasions: alone, with an antacid, during treatment with omeprazole, and within enteric coated capsules.
Results—When BIC-C difficile was taken alone, a mean (SEM) of 1033 (232) mg of bovine IgG was recovered in the ileal fluid representing 49% of the total ingested dose. Bovine IgG recovery was not significantly increased by antacid (636 (129) mg) or omeprazole (1052 (268) mg). The enteric capsules frequently remained intact or only partially opened in the ileal effluent and free bovine IgG levels were low in this treatment group (89(101) mg). Bovine IgG recovery was higher in volunteers with shorter (less than two hours) mouth to ileum transit times (68% versus 36%, p<0.05). Specific bovine IgG against C difficile toxin A was detected in ileal fluid following oral BIC. Toxin neutralising activity was also present and correlated closely with bovine IgG levels (r=0.95, p<0.001).
Conclusion—BIC-C difficile resists digestion in the human upper gastrointestinal tract and specific anti-C difficile toxin A binding and neutralising activity was retained. Passive oral immunotherapy with anti-C difficile BIC may be a useful non-antibiotic approach to the prevention and treatment of C difficile antibiotic associated diarrhoea and colitis.

Keywords: pseudomembranous colitis; toxin; diarrhoea; IgG; immunotherapy; antibiotic; Clostridium difficile

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Fekety R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 1997 May;92(5):739–750. [PubMed]
  • Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med. 1994 Jan 27;330(4):257–262. [PubMed]
  • Pothoulakis C. Pathogenesis of Clostridium difficile-associated diarrhoea. Eur J Gastroenterol Hepatol. 1996 Nov;8(11):1041–1047. [PubMed]
  • Riegler M, Sedivy R, Pothoulakis C, Hamilton G, Zacherl J, Bischof G, Cosentini E, Feil W, Schiessel R, LaMont JT, et al. Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest. 1995 May;95(5):2004–2011. [PMC free article] [PubMed]
  • Just I, Wilm M, Selzer J, Rex G, von Eichel-Streiber C, Mann M, Aktories K. The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins. J Biol Chem. 1995 Jun 9;270(23):13932–13936. [PubMed]
  • Just I, Selzer J, Wilm M, von Eichel-Streiber C, Mann M, Aktories K. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature. 1995 Jun 8;375(6531):500–503. [PubMed]
  • Borriello SP. The influence of the normal flora on Clostridium difficile colonisation of the gut. Ann Med. 1990 Feb;22(1):61–67. [PubMed]
  • Lyerly DM, Bostwick EF, Binion SB, Wilkins TD. Passive immunization of hamsters against disease caused by Clostridium difficile by use of bovine immunoglobulin G concentrate. Infect Immun. 1991 Jun;59(6):2215–2218. [PMC free article] [PubMed]
  • Kelly CP, Pothoulakis C, Vavva F, Castagliuolo I, Bostwick EF, O'Keane JC, Keates S, LaMont JT. Anti-Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotoxicity of C. difficile toxins. Antimicrob Agents Chemother. 1996 Feb;40(2):373–379. [PMC free article] [PubMed]
  • Kelly CP, Chetham S, Keates S, Bostwick EF, Roush AM, Castagliuolo I, LaMont JT, Pothoulakis C. Survival of anti-Clostridium difficile bovine immunoglobulin concentrate in the human gastrointestinal tract. Antimicrob Agents Chemother. 1997 Feb;41(2):236–241. [PMC free article] [PubMed]
  • Nord J, Ma P, DiJohn D, Tzipori S, Tacket CO. Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients. AIDS. 1990 Jun;4(6):581–584. [PubMed]
  • Davidson GP, Whyte PB, Daniels E, Franklin K, Nunan H, McCloud PI, Moore AG, Moore DJ. Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus. Lancet. 1989 Sep 23;2(8665):709–712. [PubMed]
  • Tacket CO, Losonsky G, Link H, Hoang Y, Guesry P, Hilpert H, Levine MM. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. N Engl J Med. 1988 May 12;318(19):1240–1243. [PubMed]
  • Tacket CO, Binion SB, Bostwick E, Losonsky G, Roy MJ, Edelman R. Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. Am J Trop Med Hyg. 1992 Sep;47(3):276–283. [PubMed]
  • Mietens C, Keinhorst H, Hilpert H, Gerber H, Amster H, Pahud JJ. Treatment of infantile E. coli gastroenteritis with specific bovine anti-E. coli milk immunoglobulins. Eur J Pediatr. 1979;132(4):239–252. [PubMed]
  • Brunser O, Espinoza J, Figueroa G, Araya M, Spencer E, Hilpert H, Link-Amster H, Brüssow H. Field trial of an infant formula containing anti-rotavirus and anti-Escherichia coli milk antibodies from hyperimmunized cows. J Pediatr Gastroenterol Nutr. 1992 Jul;15(1):63–72. [PubMed]
  • Brüssow H, Hilpert H, Walther I, Sidoti J, Mietens C, Bachmann P. Bovine milk immunoglobulins for passive immunity to infantile rotavirus gastroenteritis. J Clin Microbiol. 1987 Jun;25(6):982–986. [PMC free article] [PubMed]
  • Roos N, Mahé 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 May;125(5):1238–1244. [PubMed]
  • Libby JM, Jortner BS, Wilkins TD. Effects of the two toxins of Clostridium difficile in antibiotic-associated cecitis in hamsters. Infect Immun. 1982 May;36(2):822–829. [PMC free article] [PubMed]
  • Fernie DS, Thomson RO, Batty I, Walker PD. Active and passive immunization to protect against antibiotic associated caecitis in hamsters. Dev Biol Stand. 1983;53:325–332. [PubMed]
  • Kim PH, Iaconis JP, Rolfe RD. Immunization of adult hamsters against Clostridium difficile-associated ileocecitis and transfer of protection to infant hamsters. Infect Immun. 1987 Dec;55(12):2984–2992. [PMC free article] [PubMed]
  • Aronsson B, Granström M, Möllby R, Nord CE. Serum antibody response to Clostridium difficile toxins in patients with Clostridium difficile diarrhoea. Infection. 1985 May-Jun;13(3):97–101. [PubMed]
  • Johnson S, Gerding DN, Janoff EN. Systemic and mucosal antibody responses to toxin A in patients infected with Clostridium difficile. J Infect Dis. 1992 Dec;166(6):1287–1294. [PubMed]
  • Kelly CP. Immune response to Clostridium difficile infection. Eur J Gastroenterol Hepatol. 1996 Nov;8(11):1048–1053. [PubMed]
  • Leung DY, Kelly CP, Boguniewicz M, Pothoulakis C, LaMont JT, Flores A. Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr. 1991 Apr;118(4 Pt 1):633–637. [PubMed]
  • Mulligan ME, Miller SD, McFarland LV, Fung HC, Kwok RY. Elevated levels of serum immunoglobulins in asymptomatic carriers of Clostridium difficile. Clin Infect Dis. 1993 Jun;16 (Suppl 4):S239–S244. [PubMed]
  • Warny M, Vaerman JP, Avesani V, Delmée M. Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect Immun. 1994 Feb;62(2):384–389. [PMC free article] [PubMed]
  • Allo M, Silva J, Jr, Fekety R, Rifkin GD, Waskin H. Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin. Gastroenterology. 1979 Feb;76(2):351–355. [PubMed]
  • Salcedo J, Keates S, Pothoulakis C, Warny M, Castagliuolo I, LaMont JT, Kelly CP. Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut. 1997 Sep;41(3):366–370. [PMC free article] [PubMed]
  • Tjellström B, Stenhammar L, Eriksson S, Magnusson KE. Oral immunoglobulin A supplement in treatment of Clostridium difficile enteritis. Lancet. 1993 Mar 13;341(8846):701–702. [PubMed]

Figures and Tables

Figure 1
Outline of clinical study protocol.
Figure 2
Recovery of free bovine IgG from the ileum after oral administration of BIC-C difficile. Results expressed as mean (SEM); individual data points are shown. The mean recovery expressed as a percentage of the total amount of ingested bovine IgG is also ...
Figure 3
Time course of bovine IgG recovery from the ileum after oral BIC-C difficile. The mean amounts of bovine IgG recovered at each collection time are shown for each treatment group (n=5).
Figure 4
Comparison of specific anti-C difficile toxin A and total bovine IgG levels in ileal fluid after oral BIC-C difficile. (A) Levels for subject 2, receiving BIC-C difficile alone. Total recovery was 1558 mg or 74% of the ingested dose of bovine IgG. (B) ...
Figure 5
Comparison of specific anti-C difficile toxin A neutralising activity and total bovine IgG levels in ileal fluid after oral BIC-C difficile. The greatest dilution of ileal fluid which neutralised toxin A is shown together with the bovine IgG level of ...

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