Intestinal Inflammation in Children with Cystic Fibrosis Is Associated with Crohn's-Like Microbiota Disturbances.

Raphaël Enaud,Katarzyna B Hooks,Patrick Berger,Christophe Hubert,Cécile Bébéar,Philippe Lehours,Macha Nikolski,Thierry Lamireau,Stéphanie Bui,Thomas Barnetche,Michael Fayon,Thierry Schaeverbeke,Thomas Bazin,Haude Clouzeau,Marie Massot,Laurence Delhaes,Aurélien Barre

doi:10.3390/jcm8050645

Abstract

Cystic fibrosis (CF) is a systemic genetic disease that leads to pulmonary and digestive disorders. In the majority of CF patients, the intestine is the site of chronic inflammation and microbiota disturbances. The link between gut inflammation and microbiota dysbiosis is still poorly understood. The main objective of this study was to assess gut microbiota composition in CF children depending on their intestinal inflammation. We collected fecal samples from 20 children with CF. Fecal calprotectin levels were measured and fecal microbiota was analyzed by 16S rRNA sequencing. We observed intestinal inflammation was associated with microbiota disturbances characterized mainly by increased abundances of Staphylococcus, Streptococcus, and Veillonella dispar, along with decreased abundances of Bacteroides, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. Those changes exhibited similarities with that of Crohn’s disease (CD), as evidenced by the elevated CD Microbial-Dysbiosis index that we applied for the first time in CF. Furthermore, the significant over-representation of Streptococcus in children with intestinal inflammation appears to be specific to CF and raises the issue of gut–lung axis involvement. Taken together, our results provide new arguments to link gut microbiota and intestinal inflammation in CF and suggest the key role of the gut–lung axis in the CF evolution.

Highlights

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR), leading to viscous secretions accumulating on epithelial surfaces in both the lungs and the gastrointestinal tract [1]
We identified seven (35%) children with significant intestinal inflammation
With more CF patients surviving into advanced adulthood we need to improve our understanding and management of this systemic disease, including the chronic intestinal inflammation

Summary

Introduction

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR), leading to viscous secretions accumulating on epithelial surfaces in both the lungs and the gastrointestinal tract [1]. In recent decades, improved patient care in the management of pulmonary disease has led to an older CF population with new complications, including intestinal disorders [2]. In CF, this disturbed microbiota, usually named “dysbiosis”, stems from multiple factors including hydro electrolytic disruptions of the intestinal secretions, slower gastrointestinal transit time [12], drug uses, impaired innate immunity in the gut [13,14], and hypercaloric diet [15,16], and appears to be correlated with the severity of the CFTR mutations [11]

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Conclusion