A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis

F Fouhy,F Shanahan,B J Plant,R P Ross,E T Flanagan,J A Eustace,Y Mccarthy,C Shortt,C Fleming,M C Rea,A M Walsh,D M Murphy,C Stanton,O O’Sullivan,M Mccarthy,N J Ronan,M Daly

doi:10.1038/s41598-017-06880-y

Abstract

Cystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further.

Highlights

Cystic Fibrosis (CF) is an autosomal recessive disorder affecting over 70,000 individuals globally[1, 2]
We studied the microbiota composition and functionality of the CF patients compared to the controls, using the HUMAnN2 analysis pipeline
Research remains limited, on what impact such changes have on functionality and to date only one shotgun metagenomic study has been completed on the gut microbiota in children with CF, with no adult CF shotgun metagenomic study being reported

Summary

Introduction

Cystic Fibrosis (CF) is an autosomal recessive disorder affecting over 70,000 individuals globally[1, 2]. Studies using DNA based approaches, including next-generation sequencing, have shown the CF gut microbiota to be significantly different to the gut microbiota of non-CF controls[10, 11]. The majority of next-generation sequencing studies to date have relied on sequencing of the 16S rRNA bacterial gene While these approaches have provided important insights into the CF lung[15, 16] and gut microbiota[10], the functionality of the altered CF microbiome has been poorly characterised. The authors suggested that this altered functionality was diminished with age This pilot study wanted to take the first steps to investigate if there would be measurable changes to the gut microbiota functionality in an adult CF population. Metabolites and gut microbiota were significantly altered in the CF group compared to the non-CF controls

Objectives

Methods

Results

Conclusion