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Background <p>CFTR modulators such as lumacaftor/ivacaftor (LUM/IVA) may reshape microbiota-mycobiota composition in the lungs and gut. While the gut-lung axis is established in other settings, little is known about its role following modulator therapy, particularly in the 2–11 age group.</p> Methods <p>In a prospective national multicentre study, 116 children with cystic fibrosis (2–11 years) starting LUM/IVA were followed for 12 months. Stool and sputum were collected at baseline, 3, 6 and 12 months. Bacterial and fungal communities were profiled by 16S rRNA and ITS2 sequencing; diversity, dysbiosis indices, faecal and sputum calprotectin, and gut–lung microbial networks were analysed.</p> Results <p>LUM/IVA was associated with increased bacterial diversity and compositional shifts in gut and lung microbiota, alongside a significant reduction in faecal calprotectin. Airway mycobiota diversity remained stable. Two lung microbiome response profiles emerged: “responders” (greater bacterial diversity gain) and “non-responders” (minimal change). Baseline gut and lung composition predicted these profiles with 81% accuracy in a random-forest model. Inter-organ microbial interactions peaked at 3 months after initiation and then diverged between profiles, indicating distinct gut–lung axis remodelling.</p> Conclusion <p>LUM/IVA influences gut-lung microbiota-mycobiota dynamics, with heterogeneous responses between paediatric patients. Identifying factors predictive of response is a key future challenge.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>In 116 children aged 2–11, lumacaftor/ivacaftor reshaped gut and lung microbiota and reduced fecal calprotectin over 12 months.</p> </ItemContent> <ItemContent> <p>First pediatric multicenter study integrating bacterial and fungal profiling of stool and sputum with gut–lung network analyses; identifies two distinct lung microbiome response profiles.</p> </ItemContent> <ItemContent> <p>Baseline gut and lung composition predicted the response profile with approximately 81% accuracy.</p> </ItemContent> <ItemContent> <p>Highlights a 3-month interaction peak and baseline profiling as practical markers to guide monitoring and microbiome-informed precision care.</p> </ItemContent> </UnorderedList></p>

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Gut–lung microbial dynamics with lumacaftor/ivacaftor in children with cystic fibrosis: a prospective multicenter study

  • 期刊论文

  • 发表日期：

    2026年2月5日

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  • Florian Lussac-Sorton,
  • Jayanth Kumar Narayana,
  • Nathalie Wizla,
  • Aurélie Tatopoulos,
  • Mélissa Baravalle,
  • Léa Rotidis,
  • Véronique Houdoin,
  • Catherine Llerena,
  • Philippe Reix,
  • Isabelle Sermet,
  • Jeanne Languepin,
  • Elena Charpentier,
  • Maxime Lefranc,
  • Préscillia Alves Gomes,
  • Stéphanie Bui,
  • Fabien Beaufils,
  • Patrick Berger,
  • Sanjay H. Chotirmall,
  • Laurence Delhaes,
  • Raphael Enaud

摘要

Background

CFTR modulators such as lumacaftor/ivacaftor (LUM/IVA) may reshape microbiota-mycobiota composition in the lungs and gut. While the gut-lung axis is established in other settings, little is known about its role following modulator therapy, particularly in the 2–11 age group.

Methods

In a prospective national multicentre study, 116 children with cystic fibrosis (2–11 years) starting LUM/IVA were followed for 12 months. Stool and sputum were collected at baseline, 3, 6 and 12 months. Bacterial and fungal communities were profiled by 16S rRNA and ITS2 sequencing; diversity, dysbiosis indices, faecal and sputum calprotectin, and gut–lung microbial networks were analysed.

Results

LUM/IVA was associated with increased bacterial diversity and compositional shifts in gut and lung microbiota, alongside a significant reduction in faecal calprotectin. Airway mycobiota diversity remained stable. Two lung microbiome response profiles emerged: “responders” (greater bacterial diversity gain) and “non-responders” (minimal change). Baseline gut and lung composition predicted these profiles with 81% accuracy in a random-forest model. Inter-organ microbial interactions peaked at 3 months after initiation and then diverged between profiles, indicating distinct gut–lung axis remodelling.

Conclusion

LUM/IVA influences gut-lung microbiota-mycobiota dynamics, with heterogeneous responses between paediatric patients. Identifying factors predictive of response is a key future challenge.

Impact

In 116 children aged 2–11, lumacaftor/ivacaftor reshaped gut and lung microbiota and reduced fecal calprotectin over 12 months.

First pediatric multicenter study integrating bacterial and fungal profiling of stool and sputum with gut–lung network analyses; identifies two distinct lung microbiome response profiles.

Baseline gut and lung composition predicted the response profile with approximately 81% accuracy.

Highlights a 3-month interaction peak and baseline profiling as practical markers to guide monitoring and microbiome-informed precision care.