Longitudinal dynamics of gut plasmidome and antibiotic resistance during antibiotic therapy: a case report

Abstract

The human gut microbiome is composed of diverse microbes, and its association with human health is well-recognized. Antibiotic therapies for treating infectious diseases often mediate adverse influences on gut microbial ecosystems. Further, ESBL (extended-spectrum beta-lactamase)-producing bacteria potentially residing in the gut benefit from antibiotic-induced environmental changes via positive selection for resistance traits. As antimicrobial resistance (AMR) genes are often harbored by mobile plasmids, the importance of these extrachromosomal mobile genetic elements during antibiotic exposure is evident. However, there is still a knowledge gap in how microbiomes respond to antibiotic treatment especially in terms of plasmid carriage and how gut plasmid populations evolve following and revive after antibiotic therapy. To address these questions, in this case report we investigated the changes in plasmid population in the gut microbiome of a single ESBL-carrying patient during antibiotic therapy for uncomplicated acute appendicitis. Employing longitudinal sampling, we collected E. coli strains and performed metagenomic analysis before, during, and after the treatment. Our findings indicate that the antibiotic treatment is associated with a transient alteration in the microbial composition, AMR profile, and plasmid population. An extensive but temporary domination of ESBL-E. coli within the gut microbiome was observed parallel to the ongoing antibiotic treatment. However, this was not sustained in the follow-up period, indicating a slight restoration of both the microbial composition and the plasmid population. The research underscores the temporary impact of antibiotic therapy on the dynamics of the gut plasmidome which essentially mediate the spread of AMR within the gut microbiome.