Table_1_Deciphering Resistome in Patients With Chronic Obstructive Pulmonary Diseases and Clostridioides difficile Infections.DOCX

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.

抗生素可改变肠道微生物群，导致菌群失调，进而产生耐药性微生物。不同的抗生素给药模式导致人类肠道中细菌组成和耐药组的不同。本研究全面调查了抗生素耐药基因（ARGs）的分布、细菌组成和抗生素治疗之间的关系，这些关系存在于慢性阻塞性肺疾病（COPD）和艰难梭菌感染（CDI）患者中，他们长期或急性间歇使用抗生素。本研究将COPD患者与26名CDI患者以及61名健康个体进行了比较。COPD病人在采集粪便前未使用抗生素的中位时间为40天（Q1: 9.5天；Q3: 60天），而CDI患者未使用抗生素的天数为0天（Q1: 0天；Q3: 0.3天）。通过中位数Bray-Curtis指数测量的组内β多样性在健康个体中最低（0.55），其次是COPD组（0.69）和CDI组（0.72）。组间β多样性在健康个体和CDI组之间最高（中位数指数=0.89）。通过每千碱基每百万读数（RPKM）测量的ARGs丰度为健康组684.2；COPD组1,215.2；CDI组2,025.1。它与细菌组成的α多样性呈负相关。在常见的ARGs类群中，健康个体氨基糖苷类、β-内酰胺类和宏量霉素-林可酰胺-链阳菌素（MLS）耐药基因的多样性和丰度最低，其次是COPD和CDI组。肠球菌和埃希菌属的丰度与ARGs丰度和抗生素治疗天数呈正相关，而双歧杆菌和瘤胃球菌则表现出负相关。此外，我们还利用宏基因组测序数据分析了氨基糖苷类和β-内酰胺类耐药基因载体之间的移动组模式。总之，与健康个体相比，CDI和COPD组中的ARGs显著增加。特别是，氨基糖苷类和β-内酰胺类耐药基因在CDI和COPD组中更为丰富，但使此类基因转移成为可能的占主导地位的移动遗传元件在各组中的流行模式相似。