Deciphering Resistome in Patients With Chronic Obstructive Pulmonary Diseases and Clostridioides difficile Infections

Abstract

Antibiotics alter the gut microbiome and cause dysbiosis leading to antibiotic-resistant organisms. Different patterns of antibiotic administration cause a difference in bacterial composition and resistome in the human gut. We comprehensively investigated the association between the distribution of antibiotic resistance genes (ARGs), bacterial composition, and antibiotic treatments in patients with chronic obstructive pulmonary diseases (COPD) and Clostridioides difficile infections (CDI) who had chronic or acute intermittent use of antibiotics and compared them with healthy individuals. We analyzed the gut microbiomes of 61 healthy individuals, 16 patients with COPD, and 26 patients with CDI. The COPD patients were antibiotic-free before stool collection for a median of 40 days (Q1: 9.5; Q3: 60 days), while the CDI patients were antibiotic-free for 0 days (Q1: 0; Q3: 0.3). The intra-group beta diversity measured by the median Bray-Curtis index was the lowest for the healthy individuals (0.55), followed by the COPD (0.69) and CDI groups (0.72). The inter-group beta diversity was the highest among the healthy and CDI groups (median index = 0.89). The abundance of ARGs measured by the number of reads per kilobase per million reads (RPKM) was 684.2; 1,215.2; and 2,025.1 for the healthy, COPD, and CDI groups. It was negatively correlated with the alpha diversity of bacterial composition. For the prevalent ARG classes, healthy individuals had the lowest diversity and abundance of aminoglycoside, β-lactam, and macrolide-lincosamide-streptogramin (MLS) resistance genes, followed by the COPD and CDI groups. The abundances of Enterococcus and Escherichia species were positively correlated with ARG abundance and the days of antibiotic treatment, while Bifidobacterium and Ruminococcus showed negative correlations for the same. In addition, we analyzed the mobilome patterns of aminoglycoside and β-lactam resistance gene carriers using metagenomic sequencing data. In conclusion, the ARGs were significantly enhanced in the CDI and COPD groups than in healthy individuals. In particular, aminoglycoside and β-lactam resistance genes were more abundant in the CDI and COPD groups, but the dominant mobile genetic elements that enable the transfer of such genes showed similar prevalence patterns among the groups.