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

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.

The Cross-Talk Between Gut Microbiota and Lungs in Common Lung Diseases

“…In stable adults with cystic fibrosis, the altered intestinal microbiota functionality has also been demonstrated (Duytschaever et al, 2013;Huang and LiPuma, 2016;Fouhy et al, 2017;Vernocchi et al, 2017). Significantly decreased Bacteroidetes and increased Firmicutes were observed in cystic fibrosis adults (Burke et al, 2017;Fouhy et al, 2017).…”

“…In stable adults with cystic fibrosis, the altered intestinal microbiota functionality has also been demonstrated (Duytschaever et al, 2013;Huang and LiPuma, 2016;Fouhy et al, 2017;Vernocchi et al, 2017). Significantly decreased Bacteroidetes and increased Firmicutes were observed in cystic fibrosis adults (Burke et al, 2017;Fouhy et al, 2017). By fecal proteomics study, it was demonstrated that the abundances of Ruminococcus gnavus, Enterobacteriaceae, and Clostridia species was increased while butyrate reducers Faecalibacterium prausnitzii was decreased in patients with cystic fibrosis (Debyser et al, 2016).…”

“…Pathway abundances and gene families involved in unsaturated fatty acid biosynthesis and pathway of xenobiotic metabolism were higher in cystic fibrosis adults compared to that of healthy controls (Fouhy et al, 2017). Furthermore, remarkable differences in the metabolites from gut microbiota also occurred between cystic fibrosis patient and healthy controls (Fouhy et al, 2017).…”

“…By fecal proteomics study, it was demonstrated that the abundances of Ruminococcus gnavus, Enterobacteriaceae, and Clostridia species was increased while butyrate reducers Faecalibacterium prausnitzii was decreased in patients with cystic fibrosis (Debyser et al, 2016). Pathway abundances and gene families involved in unsaturated fatty acid biosynthesis and pathway of xenobiotic metabolism were higher in cystic fibrosis adults compared to that of healthy controls (Fouhy et al, 2017). Furthermore, remarkable differences in the metabolites from gut microbiota also occurred between cystic fibrosis patient and healthy controls (Fouhy et al, 2017).…”

“…Cystic fibrosis is a genetic disease that affects mostly the lungs and digestive system (Haack et al, 2013). Increasing evidence shows a link between gastrointestinal microbiota and progression of lung disease in cystic fibrosis (Schippa et al, 2013;Li and Somerset, 2014;Nielsen et al, 2016;Rogers et al, 2016;Burke et al, 2017;Fouhy et al, 2017) (Figure 4). In infants with cystic fibrosis, alpha diversity was not increased over the first year of life as expected in control cohort, while the beta diversity of these two cohorts was significantly different, associating with airway exacerbations (Antosca et al, 2019).…”