Role of volatile fatty acids in colonization resistance to Clostridium difficile

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Abstract
The in vitro inhibition of Clostridium difficile by volatile fatty acids was correlated with the pH and concentrations of volatile fatty acids in the ceca of hamsters of different ages. The concentrations of cecal volatile fatty acids increased with the age of the animals. Maximum concentrations of individual volatile fatty acids were attained when the animals were ca. 19 days old, with acetic, propionic, and butyric acids occurring in the highest concentrations (72, 16, and 32 microequivalents/g of cecum, respectively). The cecal pH was approximately the same in hamsters of all ages (pH 6.6 to 7.0). Only butyric acid reached a concentration in the ceca of hamsters which was inhibitory to the in vitro multiplication of C. difficile. This inhibitory concentration was attained when the animals were ca. 19 days of age. When mixtures of volatile fatty acids were prepared at concentrations equal to those present in the ceca of hamsters, there was a direct correlation between the in vitro inhibitory activity of the volatile fatty acids and the susceptibility of hamsters 4 days of age or older to C. difficile intestinal colonization. The resistance of hamsters less than 4 days of age to C. difficile intestinal colonization appears to be due to factors other than volatile fatty acids.