American Journal of Clinical Nutrition, Vol 25, 1433-1440, Copyright © 1972 by The American Society for Clinical Nutrition, Inc.

Shigella, indigenous flora interactions in mice

¹ From the Department of Microbiology, University of Missouri School of Medicine, Columbia, Missouri 65201

Our experiments indicate that human strains of Bacteroides, Bifidobacteria, enterococci, and E. coli will monoassociate in germfree mice. Of these normal flora species, only E. coli significantly antagonized the pathogen in vivo. The low level of Shigella in the ceca of these E. coli-associated mice may represent the carrier state in human beings. At these low population levels, Shigella was recovered from the entire gastrointestinal tract of the gnotobiotic mice, but not from blood, liver, or spleen. Shigella was isolated in highest density from the ileocecal junction, and was intimately associated with the gut wall throughout the intestines. E. coli, on the other hand, was not associated with the gut wall, but was predominantly found in the lumen.

Gnotobiotic mice associated with both Bacteroides and E. coli reduced Shigella in the ceca to levels below detection. The continuous administration of streptomycin eliminated Bacteroides from the ceca, reduced the E. coli population and caused Shigella to reappear at high population levels. An apparent E. coli-Shigella recombinant appeared in vivo that possessed some biochemical characteristics of E. coli but serologically was characterized as Shigella. These studies implicate the evolution of enteric pathogens.

The mechanism of Shigella inhibition by acetic acid in vitro was found to interfere with metabolism but not with the active transport of carbohydrates. Metabolism within Shigella cells was antagonized by both dissociated and undissociated acid molecules. Cells were permeated, however, by only the undissociated form of the volatile fatty acid that predominates at lower pH levels. Physiological levels of volatile fatty acids and pH under in vivo conditions may significantly inhibit Shigella multiplication.

In conventional mice, a Shigella carrier state was observed virtually identical to the Shigella populations found in E. coil-colonized, gnotobiotic mice. The environmental conditions in the ceca of normal and germfree mice were found to be considerably different. Studies using germfree cecal contents that were adjusted to simulate conditions observed in conventional animals indicate that the low E_h and pH and the high volatile fatty acid concentration in the cecal contents of conventional animals are responsible for the inhibition of Shigella flexneri multiplication in vivo.

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