Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1969 Sep 1;130(3):659–670. doi: 10.1084/jem.130.3.659

SMALL INTESTINAL MUCOSAL CELL PROLIFERATION AND BACTERIAL FLORA IN THE CONVENTIONALIZATION OF THE GERMFREE MOUSE

Kenneth A Khoury 1, Martin H Floch 1, Theodore Hersh 1
PMCID: PMC2138714  PMID: 4896909

Abstract

The relationship between intestinal colonization and the small bowel mucosal cellular proliferation rate during conventionalization of the germfree mouse was examined. 16 mice were maintained under standard germfree conditions, and 54 others were conventionalized. Migration of the small bowel epithelial cells was followed by radioautography with administration of tritiated thymidine. Colonization was followed by qualitative and quantitative bacteriological fecal analyses. The percentages of the villi labeled (as determined by cell count) 24, 48, and 72 hr following thymidine administration showed immediate progression in the conventionalized animals from the germfree villus migration time (4 days) toward the conventional villus migration time (2 days). The epithelial migration rate of animals conventionalized for 8 days was comparable to that of conventional animals. After conventionalization, aerobic and anaerobic organisms undergo a period of extensive multiplication; however, 72 hr later the number of these microorganisms cultured in the stool decrease and are similar to those recovered from normal animals. Coliforms and streptococci are recovered in large numbers only in the first days after conventionalization, while the Bacteroides are first recovered in significant numbers on the fifth day of conventionalization. Except for smaller numbers of Bacteroides, the bacterial populations in the stools of the conventionalized animals are qualitatively and quantitatively similar by the eighth day of conventionalization to those of true conventional mice. Adaptive balance between cell proliferation and sloughing, and thus migration rate, begins immediately after conventionalization of germfree animals as bacterial populations establish themselves throughout the gastrointestinal tract, and results in a doubling of the mucosal cell turnover after 8 days. At this time both the small intestinal epithelial cell migration rate and the intestinal microflora are similar to those of conventional animals.

Full Text

The Full Text of this article is available as a PDF (900.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABRAMS G. D., BAUER H., SPRINZ H. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest. 1963 Mar;12:355–364. [PubMed] [Google Scholar]
  2. ABRAMS G. D., SCHNEIDER H., FORMAL S. B., SPRINZ H. CELLULAR RENEWAL AND MUCOSAL MORPHOLOGY IN EXPERIMENTAL ENTERITIS. INFECTION WITH SALMONELLA TYPHIMURIUM IN THE MOUSE. Lab Invest. 1963 Dec;12:1241–1248. [PubMed] [Google Scholar]
  3. Carter D., Einheber A., Bauer H. Bacterial colonization of intestine of germfree rats with external esophageal fistula after specific bacterial contamination. Surg Forum. 1965;16:79–80. [PubMed] [Google Scholar]
  4. Colwell E. J., Welsh J. D., Legters L. J., Proctor R. F. Jejunal morphological characteristics in South Vietnamese residents. JAMA. 1968 Dec 2;206(10):2273–2276. [PubMed] [Google Scholar]
  5. Dubos R. J., Savage D. C., Schaedler R. W. The indigenous flora of the gastrointestinal tract. Dis Colon Rectum. 1967 Jan-Feb;10(1):23–34. doi: 10.1007/BF02617382. [DOI] [PubMed] [Google Scholar]
  6. Floch M. H., Gershengoren W., Freedman L. R. Methods for the quantitative study of the aerobic and anaerobic intestinal bacterial flora of man. Yale J Biol Med. 1968 Aug;41(1):50–61. [PMC free article] [PubMed] [Google Scholar]
  7. GORDON H. A., BRUCKNER-KARDOSS E. Effect of normal microbial flora on intestinal surface area. Am J Physiol. 1961 Jul;201:175–178. doi: 10.1152/ajplegacy.1961.201.1.175. [DOI] [PubMed] [Google Scholar]
  8. Heneghan J. B. Imbalance of the normal microbial flora. The germ-free alimentary tract. Am J Dig Dis. 1965 Oct;10(10):864–869. doi: 10.1007/BF02236095. [DOI] [PubMed] [Google Scholar]
  9. Kenworthy R., Allen W. D. Influence of diet and bacteria on small intestinal morphology, with special reference to early weaning and Escherichia coli. Studies with germfree and gnotobiotic pigs. J Comp Pathol. 1966 Jul;76(3):291–296. doi: 10.1016/0021-9975(66)90009-0. [DOI] [PubMed] [Google Scholar]
  10. Khoury K. A., Floch M. H., Herskovic T. Effects of neomycin and penicillin administration on mucosal proliferation of the mouse small intestine. With morphological and functional correlations. J Exp Med. 1969 May 1;129(5):1063–1078. doi: 10.1084/jem.129.5.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klipstein F. A., Samloff I. M., Schenk E. A. Tropical sprue in Haiti. Ann Intern Med. 1966 Mar;64(3):575–594. doi: 10.7326/0003-4819-64-3-575. [DOI] [PubMed] [Google Scholar]
  12. LEBLOND C. P., MESSIER B. Renewal of chief cells and goblet cells in the small intestine as shown by radioautography after injection of thymidine-H3 into mice. Anat Rec. 1958 Nov;132(3):247–259. doi: 10.1002/ar.1091320303. [DOI] [PubMed] [Google Scholar]
  13. LESHER S., FRY R. J., KOHN H. I. Age and the generation time of the mouse duodenal epithelial cell. Exp Cell Res. 1961 Aug;24:334–343. doi: 10.1016/0014-4827(61)90436-0. [DOI] [PubMed] [Google Scholar]
  14. LESHER S., WALBURG H. E., Jr, SACHER G. A., Jr GENERATION CYCLE IN THE DUODENAL CRYPT CELLS OF GERM-FREE AND CONVENTIONAL MICE. Nature. 1964 May 30;202:884–886. doi: 10.1038/202884a0. [DOI] [PubMed] [Google Scholar]
  15. Lindenbaum J., Alam A. K., Kent T. H. Subclinical small-intestinal disease in East Pakistan. Br Med J. 1966 Dec 31;2(5530):1616–1619. doi: 10.1136/bmj.2.5530.1616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mushin R., Dubos R. Colonization of the mouse intestine with Escherichia coli. J Exp Med. 1965 Oct 1;122(4):745–757. doi: 10.1084/jem.122.4.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. PADYKULA H. A. Recent functional interpretations of intestinal morphology. Fed Proc. 1962 Nov-Dec;21:873–879. [PubMed] [Google Scholar]
  18. SCHAEDLER R. W., DUBOS R., COSTELLO R. THE DEVELOPMENT OF THE BACTERIAL FLORA IN THE GASTROINTESTINAL TRACT OF MICE. J Exp Med. 1965 Jul 1;122:59–66. doi: 10.1084/jem.122.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. SCHAEDLER R. W., DUBS R., COSTELLO R. ASSOCIATION OF GERMFREE MICE WITH BACTERIA ISOLATED FROM NORMAL MICE. J Exp Med. 1965 Jul 1;122:77–82. doi: 10.1084/jem.122.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SPRINZ H., SRIBHIBHADH R., GANGAROSA E. J., BENYAJATI C., KUNDEL D., HALSTEAD S. Biopsy of small bowel of Thai people. With special reference to recovery from Asiatic cholera and to an intestinal malabsorption syndrome. Am J Clin Pathol. 1962 Jul;38:43–51. doi: 10.1093/ajcp/38.1.43. [DOI] [PubMed] [Google Scholar]
  21. Shambaugh G. E., MacNair D. S., Beisel W. R. Small-bowel epithelial migration during a generalized nonenteric infection in the rat. Am J Dig Dis. 1967 Apr;12(4):403–408. doi: 10.1007/BF02241944. [DOI] [PubMed] [Google Scholar]
  22. Smith H. W. The development of the flora of the alimentary tract in young animals. J Pathol Bacteriol. 1965 Oct;90(2):495–513. [PubMed] [Google Scholar]
  23. The turnover and shedding of epithelial cells: Part II The shedding in the small intestine. Gut. 1961 Jun;2(2):117–118. doi: 10.1136/gut.2.2.117. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES