Sputum microbiota in adults with CF associates with response to inhaled tobramycin

Individuals with cystic fibrosis experience chronic lung infections with Pseudomonas aeruginosa. Anti-pseudomonal antibiotics such as inhaled tobramycin improves lung function and quality of life of chronically infected patients. We hypothesized that inhaled tobramycin has additional off-target effects beyond P. aeruginosa and that baseline microbiome prior to initiation of therapy is associated with subsequent patient response. One hundred and fifty-one sputum samples were collected from 41 patients before and after inhaled tobramycin initiation. Targeted 16S amplicon sequencing was used to assess the sputum microbiome. Patients demonstrated no significant changes in the microbiome pre vs post treatment initiation. However, patients that demonstrated improvements in lung function post inhaled tobramycin had a higher abundance of Staphylococcus in pre-therapy baseline samples suggesting a potential biomarker to predict patient response.

囊性纤维化（Cystic Fibrosis）患者常罹患铜绿假单胞菌（Pseudomonas aeruginosa）引发的慢性肺部感染。抗假单胞菌抗生素类药物如吸入用妥布霉素（inhaled tobramycin），可改善慢性感染患者的肺功能与生活质量。本研究提出假设：吸入用妥布霉素除对铜绿假单胞菌发挥作用外，还存在额外的脱靶效应；且治疗启动前的基线微生物组与患者后续的治疗应答存在相关性。本研究从41名患者中采集了151份痰液样本，覆盖吸入用妥布霉素治疗启动的前后时间节点。研究采用靶向16S扩增子测序（16S amplicon sequencing）技术对痰液微生物组进行分析。整体而言，患者的痰液微生物组在治疗启动前后未出现显著变化。但在吸入用妥布霉素治疗后肺功能得到改善的患者，其治疗前基线样本中的葡萄球菌（Staphylococcus）丰度显著更高，提示葡萄球菌或可作为预测患者治疗应答的潜在生物标志物。