Association found between cystic fibrosis and gut microbiota composition and functionality

Gut microbiome research has recently focused not only in gastrointestinal diseases, but also in other conditions with systemic effects beyond the gut. Cystic fibrosis (CF) is a progressive genetic disease that affects the lungs: both chloride and bicarbonate ion transport across epithelial cells in the lung are affected, but also epithelial cells located throughout the body, leading to an altered gastrointestinal homeostasis, among other things.

A recent study, led by Dr. Paul Ross from University College Cork (Cork, Ireland), has shown that CF and its antibiotic IV treatment are associated with different gut microbiota composition, when comparing individuals with CF (n = 43) to non-CF controls (n = 69). Specifically, CF patients had a decrease in Faecalibacterium, Roseburia, Akkermansia and Bifidobacterium, which are generally considered markers of a healthy gut microbiota. According to the authors, multiple factors may contribute to gut microbiota dysbiosis in patients with CF: the cystic fibrosis transmembrane conductance regulator gene mutation may result in increased mucus secretion in the small intestine -which in turn results in the accumulation of thick mucus and overgrowth of pathogenic bacteria; an unhealthy diet, the use of pancreatic enzymes, the lifelong exposure to antibiotics in those with CF and hospitalization may also contribute. Interestingly, a previous study in infants with CF showed that changes to the gut microbiota may presage changes in the lung microbiota.

The researchers also found that gut microbiota changed with progression of lung disease in those with CF, as individuals with CF who had severe lung dysfunction (% predicted forced expiratory volume in 1 s £ 40%, a measure of lung function) showed significantly reduced gut microbiome diversity relative to those with mild or moderate lung dysfunction.

Another recent study, led by Dr. Barry J. Plant from University College Cork (Cork, Ireland), has found that CF and its treatment is also associated with gut microbiota functionality in adult CF patients compared to controls.

In order to characterize the functionality of the altered CF microbiome, the researchers analysed both metagenomics DNA and metabolomics from faecal samples from 6 CF patients (aged 23-71 years, samples of whom were collected during pulmonary stability) and 6 non-CF controls (aged 20-65 years). As previously reported by the same research group, the gut microbiota of CF individuals was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. It is noteworthy that Enterococcus faecalis and Clostridium hathewayi were only identified in the CF gut microbiota and not in the controls.

Specifically, gene families and metabolic pathways involved in lipid biosynthesis-including pathways involved in unsaturated fatty acid biosynthesis, palmitoleate biosynthesis, and fatty acid oxidation- as well as metabolism of protein, carbohydrate and xenobiotics (e.g., pathways involved in toluene and aromatic compound degradation) – were significantly higher in CF patients compared to controls. It was also found that increased Ruminococcus, Clostridia, Enterococcus and Eggerthella were the main contributors to higher abundance of lipid and carbohydrate metabolism pathways.

Besides this, significant differences in several metabolites (hexadecanoic acid, myristic acid, and 9-octadecenoic acid) also occurred between the two groups. Metabolites positively correlated with the pathway abundances.

On the whole, these results support that adults with CF exhibit a dysbiosis of the gut microbiome (atypical composition and function) compared to the controls, together with significant differences in metabolite profile. The researchers also emphasized that further research focusing on gut microbiome composition and diversity across periods of pulmonary stability, exacerbation and post-exacerbation will help depict a clear picture of whether targeting the gut microbiota in those with CF could be an appropriate therapeutic strategy.

References:

Burke DG, Fouhy F, Harrison MJ, et al. The altered gut microbiota in adults with cystic fibrosis. BMC Microbiol. 2017; 17(1):58. doi: 10.1186/s12866-017-0968-8.

Fouhy F, Ronan NJ, O’Sullivan O, et al. A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis. Sci Rep. 2017; 7(1):6685. doi: 10.1038/s41598-017-06880-y.