Intervention-driven microbiome changes and antibiotic resistance accumulation in patients with cystic fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease which affects over 100,000 people worldwide. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), leading to malfunction of exocrine tissues and severe damage to the respiratory and the digestive tracts. In the last decades, improved therapeutic approaches for most of the CFTR mutations have significantly increased the life expectancy of CF patients. The frequent antibiotic interventions of these patients, however, represent an important manipulation of the microbial communities in the already biased microbiome structures in different organs. The particular effects of long-term and short-term antibiotic treatments on the compositional microbiome changes and the potential accumulation of antibiotic resistance genes (ARGs) are yet largely unknown.

In this study we performed a longitudinal analysis of the microbiome structures in the respiratory tract (nasal lavages, sputum samples) and the gastrointestinal tract (stool samples) of CF patients. Thereby the patients were divided in two different cohorts depending on disease severity and antibiotic administration (ambulant/per os (PO) vs. stationary/intravenous (IV)) and the microbiome analyses performed before and after therapeutic interventions.

High-throughput sequencing microbiome analyses revealed site-specific differences in the compositional structures of the microbial communities in both patient cohorts (PO and IV). The bacterial communities were further modulated by the therapeutic intervention in a differential manner. The presence of ARGs in the samples form CF patients was increased when compared to their relatives or a healthy control cohort. However, the amount of detected ARGs did not correlate with the cumulative antibiotic intake over the previous 3 years of therapy. The findings of this study contribute to a better understanding of the short- and long-term impact of antibiotic interventions on the microbial community structures in different organs of CF patients.

Publication History

Article published online:
09 March 2023