The Role of the Microbial Flora in Uremia

Germfree rats were used in 3 experiments to study the effects of the microbial flora on survival time after acute uremia produced by a one-stage bilateral nephrectomy. Germfree rats, limited-flora rats, and conventionalized rats (all maintained continuously in isolators) were subjected to nephrectomy or to sham nephrectomy, deprived of food and water until they died, respectively, of uremia or of starvation, and their survival times compared. To establish a limited defined flora in advance of nephrectomy, germfree rats were either monocontaminated (Staphylococcus albus), dicontaminated (S. albus and Proteus mirabilis) or tetracontaminated (S. albus, S. faecalis, P. mirabilis, and E. coli); to conventionalize germfree rats, they were exposed to the mixed microbial flora contained in the cecal contents of ordinary rats, which was the source of the aforementioned bacteria and which included other uncharacterized microorganisms as well. The intestine of all rats with a limited flora persisted in a morphologic state that was virtually no different from that of the germfree rat, including the presence of an enlarged, thin-walled cecum; by contrast, the intestine of the conventionalized rats permanently assumed the morphological characteristics of ordinary, open-laboratory rats with the cecum reduced to normal size. After nephrectomy and food and water deprivation (death from anuria): (a) All germfree rats but one outlived their conventionalized counterparts in each of the 3 experiments; the 21 germfree rats (127 hr) lived, on the average, 2 days longer than did the 24 conventionalized rats (75 hr). No sex difference was demonstrated. (b) The rats with a limited flora died correspondingly sooner as the complexity of their flora increased; survival time of the tetracontaminated rats was significantly shorter than that of the germfree rats, and statistically no different from that of the conventionalized rats. After sham nephrectomy and food and water deprivation (delayed death from starvation): (a) All rats, irrespective of microbial status or sex, outlived their fasting nephrectomized partners. The conventionalized rats endured starvation approximately 2.5 wk longer than they did anuria and the germfree rats 1 wk longer. (b) All conventionalized rats, both male and female, outlived their respective germfree counterparts by about 1 wk. (c) All males, irrespective of microbial status, survived longer than did the females; the average difference was 4 days. The differences in tolerance to anuria or starvation did not correlate with initial body weight or rate of weight loss.