The altered gut microbiota in adults with cystic fibrosis

Abstract

Background: Cystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed.

Results: The CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV₁ (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV₁ ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (-0.383, Simpson's Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity.

Conclusions: This is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to develop CF specific probiotics to minimise microbiota alterations.

Keywords: 454-pyrosequencing; Antibiotic therapy; Cystic fibrosis; Gut microbiota; Microbial diversity.

Fig. 1

Visualisation of the PCoA analysis based on unweighted (a) and weighted (b) Unifrac distance matrices. Samples separate into 2 clusters, CF samples (red) and control samples (blue)

Fig. 2

Percentage relative abundance of phyla in those with CF compared to non-CF controls

Fig. 3

Percentage relative abundance of the 21 families that were significantly different in the CF study cohort compared to the non-CF controls

Fig. 4

Percentage relative abundance of phyla in the non-CF controls compared to the individuals with CF, stratified based on number of IV courses in the previous 12 months

Fig. 5

Correlation analysis of gut microbiota diversity and IV antibiotic courses (a Chao 1 and Simpson’s diversity index) and % predicted FEV₁ (b Chao 1 and Simpson’s diversity index; 1 = FEV₁ ≤ 40%, 2 = FEV₁ 41–69%, 3 = FEV₁ ≥ 70%). Panel c provides the correlation coefficients and p values for all diversity analysis

Fig. 6

Percentage relative abundance of significantly different genera in the controls versus the individuals with CF stratified by % predicted FEV_1. Mild lung disease was classed as % predicted FEV₁ ≥ 70%; moderate as 41–69% and severe ≤40%