WS04.02Gut microbiota-metabolome relationships across CFTR modulator usage: preliminary findings from the GRAMPUS-CF study

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.511

R. Marsh , W. Cheung , D. Arends , D. Sills , D.W. Rivett , A.R. Smyth , C. van der Gast

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引用次数: 0

Abstract

Objectives

Despite shifts to highly effective CFTR modulators, some people with cystic fibrosis (pwCF) continue to experience intestinal abnormalities, associated symptoms, and gut microbiota dysbiosis. Baseline faecal samples across children and adults in the Gut Research Advancing a Mechanistic and Personalised Understanding of Symptoms in Cystic Fibrosis (GRAMPUS-CF) study were used to investigate relationships between gut microbiota composition and the intestinal metabolome under elexacaftor/tezacaftor/ivacaftor (ETI) treatment.

Methods

Gut microbiota profile was determined using PacBio full-length 16S HiFi sequencing (n=70). Untargeted metabolomics, including additional lipidomics, were performed with ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) (n=64). Correlation-based approaches were used to construct networks highlighting relationships between taxa and metabolites across paired samples. Participant clinical data was integrated to investigate associations with microbiota structure and function.

Results

A wide array of unique metabolites from the metabolomic (n=660) and lipidomic approaches (n=527) were identified from participant faecal samples. Network analyses highlighted both positive and negative associations across beneficial and potentially pathogenic taxa, extending to relationships with metabolites and lipids of physiological interest in the CF intestine. Clinical demographics also explained the variance observed across microbiota structure, alongside metabolomic and lipidomic profiles.

Conclusions

Faecal multi-omics indicate important relationships with gut microbiota structure across pwCF undertaking CFTR modulator therapy. Temporal dynamics of the gut microbiome across these participants will be investigated across ETI therapy in the GRAMPUS-CF study. Further clinical data, participant symptomatic data, and intestinal physiology metrics will support our future analyses.

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肠道微生物群-代谢组在CFTR调节剂使用中的关系：来自GRAMPUS-CF研究的初步发现

尽管已转向高效CFTR调节剂，但一些囊性纤维化（pwCF）患者仍会出现肠道异常、相关症状和肠道微生物群失调。在肠道研究中，儿童和成人的基线粪便样本促进了对囊性纤维化症状的机制和个性化理解（GRAMPUS-CF）研究被用来调查肠道微生物群组成和肠道代谢组在elexaftor /tezacaftor/ivacaftor （ETI）治疗下的关系。方法采用PacBio全长度16S HiFi测序法测定70例患者的肠道菌群。非靶向代谢组学，包括额外的脂质组学，采用超高效液相色谱-高分辨率质谱（UHPLC-HRMS）进行（n=64）。基于相关性的方法被用来构建网络，突出分类群和代谢物在成对样本之间的关系。研究人员整合了参与者的临床数据，以调查与微生物群结构和功能的关系。结果从参与者的粪便样本中鉴定出代谢组学（n=660）和脂质组学（n=527）的一系列独特代谢物。网络分析强调了有益和潜在致病分类群之间的正相关和负相关，延伸到CF肠中代谢产物和生理兴趣脂质的关系。临床人口统计学也解释了在微生物群结构、代谢组学和脂质组学概况中观察到的差异。结论粪便多组学表明，接受CFTR调节剂治疗的pwCF与肠道菌群结构有重要关系。在GRAMPUS-CF研究中，这些参与者的肠道微生物组的时间动态将在ETI治疗中进行研究。进一步的临床数据、参与者症状数据和肠道生理指标将支持我们未来的分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.