Colonization resistance of the human intestinal microflora: Testing the hypothesis in normal volunteers

  • S. L. Gorbach
  • M. Barza
  • M. Giuliano
  • N. V. Jacobus
Current Topic: Review


Colonization resistance is the mechanism whereby the intestinal microflora protects itself against incursion by new and often harmful microorganisms. Some authors have claimed that colonization resistance is related to the integrity of the anaerobic flora, but this point has not been established in humans. In previous studies in our laboratory cefoxitin, piperacillin, cefoperazone or aztreonam were administered intravenously to healthy volunteers in order to study changes in the intestinal flora and acquisition of new strains. Seven of 16 antibiotic-treated subjects were colonized with gram-negative bacilli, but no correlation was observed between this colonization and the suppression of either anaerobes or any other component of the fecal flora. Marked strains ofEscherichia coli andPseudomonas aeruginosa were also administered by mouth in order to test acquisition of new bacteria. The fed bacteria were found in the stools of both antibiotic-treated and control subjects; the antibiotics had no apparent influence on the ability of these strains to colonize the intestinal tract. Our work, along with findings of others, supports the concept that colonization resistance occurs in humans and is diminished by antibiotic administration. However, it does not support the hypothesis that colonization resistance is related to the anaerobic microflora.


Healthy Volunteer Intestinal Tract Normal Volunteer Piperacillin Cefoxitin 
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  1. 1.
    Kager, L., Ljungdahl, I., Malmborg, A. S., Nord, C. E., Pieper, R., Dahlgren, P. Antibiotic prophylaxis with cefoxitin in colorectal surgery. Annals of Surgery 1981, 193: 277–282.Google Scholar
  2. 2.
    Mulligan, M. E., Citron, D. M., McNamara, B. T., Finegold, S. M. Impact of cefoperazone therapy on fecal flora. Antimicrobial Agents and Chemotherapy 1982, 22: 226–230.Google Scholar
  3. 3.
    Kager, L., Malmborg, A. S., Nord, C. E., Sjostedt, S. The effect of piperacillin prophylaxis on the colonic microflora in patients undergoing colorectal surgery. Infection 1983, 11: 251–254.Google Scholar
  4. 4.
    Bodey, G. P., Fainstein, V., Garcia, I., Rosenbaum, B., Wong, Y. Effect of broad-spectrum cephalosporins on the microbial flora of recipients. Journal of Infectious Diseases 1983, 148: 892–897.Google Scholar
  5. 5.
    Mulligan, M. E., Citron, D., Gabay, E., Kirby, B. D. George, E. L., Finegold, S. M. Alterations in human fecal flora, including ingrowth ofClostridium difficile, related to cefoxitin therapy. Antimicrobial Agents and Chemotherapy 1984, 26: 343–346.Google Scholar
  6. 6.
    Nord, C. E., Kager, L., Heimdahl, A. Impact of antimicrobial agents on the gastrointestinal microflora and the risk of infections. American Journal of Medicine 1984, 76 (5A): 99–106.Google Scholar
  7. 7.
    Abrams, G. D., Bishop, J. E. Effect of the normal microbial flora on the resistance of the small intestines to infection. Journal of Bacteriology 1966, 92: 1604–1608.Google Scholar
  8. 8.
    Schimpff, S. C., Young, V. M., Greene, W. H., Vermeulen, M., Moody, R., Wiernik, P. H. Origin of infection in acute nonlymphocytic leukemia: significance of hospital acquisition of potential pathogens. Annals of Internal Medicine 1972, 77: 707–714.Google Scholar
  9. 9.
    van der Waaij, D., de Vries Berghuis, J. M. Determination of the colonization resistance of the digestive tract of individual mice. Journal of Hygiene 1974, 72: 379–387.Google Scholar
  10. 10.
    van der Waaij, D. Colonization resistance of the digestive tract: clinical consequences and implications. Journal of Antimicrobial Chemotherapy 1982, 10: 263–270.Google Scholar
  11. 11.
    van der Waaij, D., de Vries Berghuis, J. M., Lekkerkerk van der Wees, J. E. C. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. Journal of Hygiene 1971, 69: 405–411.Google Scholar
  12. 12.
    Miller, C. P., Bohnhoff, M., Anagnostopoulos, L. Factors responsible for resistance to enteric infections: role of intestinal microflora in resistance to enteric infection. In: Publication N 6 ori (59) N 6 ori 020 (49). Office of Naval Research, Washington D. C., 1958, p. 1–4.Google Scholar
  13. 13.
    van der Vaaij, D., de Vries Berghuis, J. M., Lekkerkerk van der Wees, J. E. C. Colonization resistance of the digestive tract in mice during systemic antibiotic treatment. Journal of Hygiene 1972, 70: 605–610.Google Scholar
  14. 14.
    Welling, G. W., Groen, G., Tuinte, J. M., Koopman, J. P., Kennis, H. M. Biochemical effects on germ-free mice of association with several strains of anaerobic bacteria. Journal of General Microbiology 1980, 117: 57–63.Google Scholar
  15. 15.
    Freter, R., Abrams, G. D. Function of various intestinal bacteria in converting germ-free mice to the normal state. Infection and Immunity 1972, 6: 119–126.Google Scholar
  16. 16.
    Koopman, J. P., Welling, G. W., Huybregts, A. W. M., Mullink, J. W. M. A., Prins, R. A. Association of germ-free mice with intestinal microfloras. Zeitschrift für Versuchstierkunde 1981, 23: 145–154.Google Scholar
  17. 17.
    Hentges, D.J. Role of the intestinal microflora in host defense against infection. In: Hentges, D. J. (ed.): Human intestinal microflora in health and disease. Academic Press, New York, 1983, p. 311–332.Google Scholar
  18. 18.
    Hentges, D. J., Stein, A. J., Casey, S. W., Que, J. W. Protective role of intestinal flora against infection withPseudomonas areruginosa in mice: influence of antibiotics on colonization resistance. Infection and Immunity 1985, 47: 118–122.Google Scholar
  19. 19.
    Giuliano, M., Barza, M., Jacobus, N. V., Gorbach, S. L.: Effect of broad-spectrum parenteral antibiotics on the composition of the intestinal microflora of humans. Antimicrobial Agents and Chemotherapy 1987, 202–206.Google Scholar
  20. 20.
    Barza, M., Guiliano, M., Jacobus, N. V., Gorbach, S. L. Effect of broad-spectrum parenteral antibiotics on “colonization resistance” of the intestinal microflora of humans. Antimicrobial Agents and Chemotherapy 1987, 31: 723–727.Google Scholar
  21. 21.
    Chang, T. W., Lauermann, M., Bartlett, J. G. Cytotoxicity assay in antibiotic-associated colitis. Journal of Infectious Diseases 1979, 140: 765–770.Google Scholar
  22. 22.
    Guiot, H. F. L., van der Meer, J. W. M., van Furth, R. Selective antimicrobial modulation of human microbial flora: infection prevention in patients with decreased host defense mechanisms by selective elimination of potentially pathogenic bacteria. Journal of Infectious Disease 1981, 143: 644–654.Google Scholar
  23. 23.
    Hargadon, M. T., Young, V. M., Schimpff, S. C., Wade, J. C., Minah, G. E. Selective suppression of alimentary tract microbial flora as prophylaxis during granulocytopenia. Antimicrobial Agents and Chemotherapy 1981, 20: 620–624.Google Scholar
  24. 24.
    Louie, T. J., Chubb, H., Bow, E. J., Conly, J. M., Harding, G. K. M., Rayner, E., James, M. Preservation of colonization resistance parameters during empiric therapy with aztreonam in the febrile neutropenic patient. Reviews of Infectious Diseases 1985, 7. Supplement 4: S747-S761.Google Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 1988

Authors and Affiliations

  • S. L. Gorbach
    • 1
  • M. Barza
    • 2
  • M. Giuliano
    • 2
  • N. V. Jacobus
    • 3
  1. 1.Department of Community HealthTufts-New England Medical CenterBoston
  2. 2.Division of Geographic-Medicine and Infectious Diseases, Department of MedicineTufts-New England Medical CenterBoston
  3. 3.Department of PathologyTufts University School of MedicineBostonUSA

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