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

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.