Anaerobic Bacteria in the Gut Microbiota Confer Colonization Resistance Against ESBL-Producing Escherichia coli in Mice

ABSTRACT Antimicrobial resistance (AMR) is a growing health concern worldwide, and gut microbiota play a significant role in its spread. This study aimed to investigate the impact of antibiotic-induced alterations in gut microbiota on the colonization of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in a mouse model. C57BL/6J mice were treated with various antibiotics (ampicillin, vancomycin, neomycin, metronidazole, or a cocktail of all four) prior to oral inoculation with ESBL-producing E. coli. 16S rRNA metagenomics analysis revealed significant alterations in gut microbiota composition and diversity following antibiotic treatment. Notably, ampicillin, vancomycin, and the antibiotic cocktail dramatically increased colonization by ESBL-producing E. coli, whereas metronidazole and neomycin treatments had minimal effects. Linear discriminant analysis highlighted that specific anaerobic bacterial groups, namely Bacteroidales, Lachnospiraceae, and Ruminococcaceae, were inversely correlated with colonization by ESBL-producing E. coli. Collectively, these findings suggest that diverse anaerobic bacteria play a crucial role in resistance against AMR bacteria colonization. This study provides insights into the complex interactions between gut microbiota and AMR colonization that could aid in the development of future strategies for risk assessment and eradication of drug-resistant bacteria. Competing Interest Statement The authors have declared no competing interest. Footnotes Authorship statement: Conceptualization: YM; Methodology: MM, YM, and DS; Validation: MM and DS; Formal Analysis: MM and DS; Investigation: MM, YM, and DS; Resources: N/A; Data Curation: YM and DS; Writing–Original Draft Preparation: MM and YM; Writing–Review and Editing: MM, YM, DS, and KY; Visualization: MM and YM; Supervision: YM and KY; Project Administration: YM; Funding acquisition: MM, YM, and KY. All authors meet the ICMJE authorship criteria.