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依伐卡托治疗对携带S1251N突变的囊性纤维化患者气道和肠道微生物群的个体及群体反应。

Individual and Group Response of Treatment with Ivacaftor on Airway and Gut Microbiota in People with CF and a S1251N Mutation.

作者信息

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

机构信息

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.

出版信息

J Pers Med. 2021 Apr 27;11(5):350. doi: 10.3390/jpm11050350.

DOI:10.3390/jpm11050350
PMID:33925519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8146888/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/8146888/c97411ff05c0/jpm-11-00350-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/8146888/4f81b4cc68a9/jpm-11-00350-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/8146888/5769007db288/jpm-11-00350-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/8146888/c97411ff05c0/jpm-11-00350-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/8146888/4f81b4cc68a9/jpm-11-00350-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/8146888/5769007db288/jpm-11-00350-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/8146888/c97411ff05c0/jpm-11-00350-g003.jpg

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Pediatr Pulmonol. 2020 Dec;55(12):3381-3383. doi: 10.1002/ppul.25065. Epub 2020 Oct 22.
2
Changes in Airway Microbiome and Inflammation with Ivacaftor Treatment in Patients with Cystic Fibrosis and the G551D Mutation.囊性纤维化和 G551D 突变患者用依伐卡托治疗后气道微生物组和炎症的变化。
Ann Am Thorac Soc. 2020 Feb;17(2):212-220. doi: 10.1513/AnnalsATS.201907-493OC.
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Front Cell Infect Microbiol. 2023 Sep 15;13:1271117. doi: 10.3389/fcimb.2023.1271117. eCollection 2023.
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Tezacaftor/Ivacaftor therapy has negligible effects on the cystic fibrosis gut microbiome.泰扎卡托/依伐卡托疗法对囊性纤维化肠道微生物群的影响可忽略不计。
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Changes in nutrition and growth status in young children in the first 12 weeks of ivacaftor therapy.依伐卡托治疗的前 12 周内婴幼儿营养和生长状况的变化。
J Cyst Fibros. 2023 Nov;22(6):989-995. doi: 10.1016/j.jcf.2023.04.010. Epub 2023 Jul 10.
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