Effect of colon flora and short-chain fatty acids on growth in vitro of Pseudomonas aeruginsoa and Enterobacteriaceae.

Heat-stable antibacterial activity in the following suspensions was demonstrated against Pseudomonas aeruginosa at pH 6.5, 6.0, and 5.5: (i) pooled colon contents of normal mice; (ii) an anaerobic, 48-h culture of normal mouse feces; and (iii) anaerobic, 48-h cultures of different bacteria from human colon flora (Escherichia coli, Bacteroides fragilis, Klebsiella pneumoniae, and Proteus mirabilis). The lower the pH of the medium, the greater was the antibacterial activity of these suspensions. The antibacterial activity of five fatty acids (propionic, butyric, isobutyric, acetic, and formic acids) was greater against P. aeruginosa than against three Enterobacteriaceae (E. coli, K. pneumoniae, and P. mirabilis) at all fatty acid concentrations (0.16 M to 0.005 M) and at the 3 pH values studied (5.5, 6.0, and 6.5). As the pH value increased, the antibacterial activity decreased. Antibacterial activity was greater at higher fatty acid concentrations, and at each pH value it was greatest for the fatty acids having high pK(a) values. Lactic acid, with the lowest pK(a), exhibited little or no antibacterial activity. Acetic and butyric acids, two of the three predominant volatile fatty acids determined by gas chromatography in the mouse colon contents and in the anaerobic culture of mouse feces, occurred in vivo in concentrations which inhibited growth of P. aeruginosa in vitro at the pH of the mouse cecum. These results suggest that undissociated short-chain fatty acids produced by the colon flora may be a mechanism of intestinal resistance to colonization by P. aeruginosa.