Effects of Antibiotics on Bacterial Species Composition and Metabolic Activities in Chemostats Containing Defined Populations of Human Gut Microorganisms

Abstract

ABSTRACT The composition and metabolic activities of the human colonic microbiota are modulated by a number of external factors, including diet and antibiotic therapy. Changes in the structure and metabolism of the gut microbiota may have long-term consequences for host health. The large intestine harbors a complex microbial ecosystem comprising several hundreds of different bacterial species, which complicates investigations on intestinal physiology and ecology. To facilitate such studies, a highly simplified microbiota consisting of 14 anaerobic and facultatively anaerobic organisms ( Bacteroides thetaiotaomicron , Bacteroides vulgatus , Bifidobacterium longum , Bifidobacterium infantis , Bifidobacterium pseudolongum , Bifidobacterium adolescentis , Clostridium butyricum , C. perfringens , C. bifermentans , C. innocuum , Escherichia coli , Enterococcus faecalis , Enterococcus faecium , Lactobacillus acidophilus ) was used in this investigation. Ampicillin [9.2 μg (ml culture) −1 ] was added to two chemostats operated at different dilution rates ( D ; 0.10 h −1 and 0.21 h −1 ), and metronidazole [76.9 μg (ml culture) −1 ] was added to a third vessel ( D = 0.21 h −1 ). Perturbations in bacterial physiology and metabolism were sampled over a 48-h period. Lactobacillus acidophilus and C. bifermentans populations did not establish in the fermentors under the imposed growth conditions. Ampicillin resulted in substantial reductions in bacteroides and C. perfringens populations at both dilution rates. Metronidazole strongly affected bacteroides communities but had no effect on bifidobacterial communities. The bacteriostatic effect of ampicillin on bifidobacterial species was growth rate dependent. Several metabolic activities were affected by antibiotic addition, including fermentation product formation and enzyme synthesis. The growth of antibiotic-resistant bifidobacteria in the large bowel may enable them to occupy ecological niches left vacant after antibiotic administration, preventing colonization by pathogenic species.