School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, USA.
Pediatr Res. 2021 Jul;90(1):99-108. doi: 10.1038/s41390-021-01419-4. Epub 2021 Mar 2.
Cystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status.
Respiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status.
The mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001).
LCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF.
Increased levels of LCFAs are found after IV antibiotic treatment in persons with CF. LCFAs have previously been associated with increased lung inflammation in asthma. This is the first report of LCFAs in the airway of persons with CF. This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF. Future studies should evaluate LCFAs as predictors of future PExs.
囊性纤维化（CF）影响全球超过 70000 人，但肺部恶化（PEx）的微生物触发因素仍不清楚。本研究的目的是确定与临床状况相关的细菌代谢途径的变化。
对 27 名住院 CF 患儿在 PEx 住院时、静脉（IV）抗生素治疗结束时和随访时采集呼吸道样本。提取细菌 DNA 并进行 shotgun DNA 测序。使用 MetaPhlAn2 和 HUMAnN2 评估细菌分类和途径相对丰度，而 DESeq2 则基于临床状况评估差异丰度。
研究参与者的平均年龄为 10 岁；85%接受联合 IV 抗生素治疗（β-内酰胺加第二种药物）。与治疗结束时相比，长链脂肪酸（LCFA）生物合成途径在随访样本中上调：庚酸（p=0.012）、油酸（p=0.048）、棕榈油酸（p=0.043）和脂肪酸延长途径（p=0.012）。与 PEx 相比，在随访中阿克洛莫伯克斯菌和埃希氏菌属也更为常见（p<0.001）。
LCFA 可能与机会性病原体的持续感染有关。未来的研究应更密切地研究肺部细菌产生 LCFA 在 CF 患者从基线健康向 PEx 转变中的作用。
在 CF 患者接受 IV 抗生素治疗后，LCFA 水平升高。LCFA 以前与哮喘中肺炎症的增加有关。这是 CF 患者气道中 LCFA 的首次报告。这项研究为细菌产生 LCFAs 可能是 CF 患者炎症的一个贡献因素提供了支持。未来的研究应评估 LCFAs 作为未来 PEx 的预测因子。
