Kristensen Maartje I, de Winter-de Groot Karin M, Berkers Gitte, Chu Mei Ling J N, Arp Kayleigh, Ghijsen Sophie, Heijerman Harry G M, Arets Hubertus G M, Majoor Christof J, Janssens Hettie M, van der Meer Renske, Bogaert Debby, van der Ent Cornelis K
Department of Pediatric Pulmonology and Allergology, Wilhelmina Children's Hospital-University Medical Center, Utrecht University, P.O. Box 85090, 3508 AB Utrecht, The Netherlands.
Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital-University Medical Center, Utrecht University, P.O. Box 85090, 3508 AB Utrecht, The Netherlands.
J Pers Med. 2021 Apr 27;11(5):350. doi: 10.3390/jpm11050350.
Ivacaftor has been shown to restore the functionality of the S1251N (also known as c.3752G>A) mutated CFTR, which may cause alterations in both airway and gut physiology and micro-environment, resulting in a change of microbiota in these organs. The aim of the present study was to analyze the effects of ivacaftor on the microbial community composition of both airway and gut in subjects with CF carrying one S1251N mutation, using a 16S rRNA gene-based sequencing approach. In 16 subjects with CF, repetitive samples from airways and gut were collected just before, and 2 months after, and, for 8 patients, also 9 and 12 months after, start of ivacaftor. 16S rRNA based sequencing identified 344 operational taxonomical units (OTUs) in a total of 139 samples (35 nasopharyngeal, 39 oropharyngeal, 29 sputum, and 36 fecal samples). Ivacaftor significantly enhanced bacterial diversity and overall microbiota composition in the gut ( < 0.01). There were no significant changes in the overall microbial composition and alpha diversity in upper and lower airways of these patients after ivacaftor treatment. Treatment with ivacaftor induces changes in gut microbiota whereas airway microbiota do not change significantly over time.
依伐卡托已被证明可恢复S1251N(也称为c.3752G>A)突变的囊性纤维化跨膜传导调节因子(CFTR)的功能,这可能会导致气道和肠道生理及微环境的改变,进而引起这些器官中微生物群的变化。本研究的目的是采用基于16S rRNA基因的测序方法,分析依伐卡托对携带一个S1251N突变的囊性纤维化患者气道和肠道微生物群落组成的影响。在16例囊性纤维化患者中,在开始使用依伐卡托之前、之后2个月,以及8例患者在开始使用依伐卡托之后9个月和12个月,收集气道和肠道的重复样本。基于16S rRNA的测序在总共139个样本(35个鼻咽样本、39个口咽样本、29个痰液样本和36个粪便样本)中鉴定出344个可操作分类单元(OTU)。依伐卡托显著提高了肠道细菌多样性和整体微生物群组成(<0.01)。依伐卡托治疗后,这些患者上、下呼吸道的整体微生物组成和α多样性没有显著变化。依伐卡托治疗可引起肠道微生物群的变化,而气道微生物群随时间没有显著变化。