Long-Term Antibiotic Use and Accumulation of Antimicrobial Resistance Genes in the Microbiome? Insights from a Cystic Fibrosis Cohort

The long-term use of antibiotics is widely assumed to contribute to the accumulation of antimicrobial resistance genes (ARGs) within the human microbiota. This assumption is largely based on studies linking antibiotic overuse to the selection of resistant bacterial strains, as well as metagenomic analyses across populations with varying antibiotic consumption. However, there remains a critical lack of longitudinal and targeted studies that quantify the accumulation of resistance determinants in relation to specific antibiotics or chronically treated patient cohorts. To address this gap, we conducted a comprehensive microbiome analysis of respiratory (nasal lavages) and gastrointestinal (stool) samples from one of the patient populations with the highest chronic antibiotic exposure: individuals with cystic fibrosis (CF). Using a well-defined CF cohort recruited prior to the introduction of modern CFTR modulator therapies, we assessed both microbial community composition and the prevalence of antimicrobial resistance genes (ARGs). Detailed antibiotic usage data were extracted from clinical records over a 3-year period and correlated with ARG profiles using regression models. Thereby, analyses were stratified by the route of antibiotic administration (oral, intravenous, and inhaled) and healthy individuals and household contacts served as comparative controls. Our findings offer critical insights into the relationship between antibiotic exposure and resistance gene accumulation in distinct body sites in CF patients. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany