The expansion of culturable opportunistic pathogens and antibiotic resistance in mouse gut following antibiotic exposure

Antibiotics significantly change gut microbiota, leading to dysbiosis and changes in bacterial community composition, which further results in a series of dysfunctions with severe health consequences. This work employed both culture-dependent and -independent methods to examine antibiotic-induced changes in gut microbiota at higher resolution using mouse models. By following bacterial changes and antibiotic resistance daily before antibiotic exposure, after antibiotic exposure, and during recovery, several significant novel findings were made. Ampicillin (AMP) and imipenem (IPM) treatment led to an acute, exponential, but temporary bloom in absolute abundances of live opportunistic pathogens Enterobacteriaceae and <i>Enterococcus</i>, while not affecting potentially beneficial <i>Lactobacillus</i>. The absolute abundances of antibiotic-resistant opportunistic pathogens followed a similar pattern. Impact on antibiotic resistance, on the other hand, is significant and persistent. Nearly, all Enterobacteriaceae performed AMP-resistant at the end of treatment with AMP, and almost 10% of <i>Enterococcus</i> became IPM-resistant following treatment with IPM. Further analysis of the genomes of isolated bacteria suggested that the former was due to replacement of Enterobacteriaceae strains while the latter is not. These studies show that antibiotic exposure led to expansion of gastrointestinal pathogens and their resistance to antibiotics, increasing risks for bacterial infections, contrary to the traditional anti-infection functions of antibiotics.IMPORTANCEThe antibiotic therapy is the primary method for treating and preventing bacterial infections. However, the consumption of antibiotics may also cause collateral damage in the normal microbial flora in human body, leading to dysbiosis with unwanted consequences. This impact was previously studied mostly with sequencing-based methods, which did not distinguish between live and dead cells, and did not provide absolute quantitative data, limiting the physiological relevance of discoveries. This work expands the methods in studying the side effects of antibiotic therapy by including culturing methods that measure absolute quantities of live bacteria. Surprising findings were made that antibiotic uptake can lead to temporary exponential bloom of opportunistic pathogens in mouse gut, and a permanent change of antimicrobial resistance in these pathogens. These findings expand our knowledge on how antibiotic therapy can affect our health and urges caution on casual antibiotic usage.