Diet and the gut-lung axis in cystic fibrosis - direct & indirect links

Abstract

Cystic fibrosis (CF) is a multisystem, autosomal, recessive disease primarily affecting the lungs, pancreas, gastrointestinal tract, and liver. Whilst there is increasing evidence of a microbial 'gut-lung axis' in chronic respiratory conditions, there has been limited analysis of such a concept in CF. We performed a comprehensive dietary and microbiota analysis to explore the interactions between diet, gastrointestinal microbiota, respiratory microbiota, and clinical outcomes in children with CF. Our results demonstrate significant alterations in intestinal inflammation and respiratory and gastrointestinal microbiota when compared to age and gender matched children without CF. We identified correlations between the gastrointestinal and respiratory microbiota, lung function, CF pulmonary exacerbations and anthropometrics, supporting the concept of an altered gut-lung axis in children with CF. We also identified significant differences in dietary quality with CF children consuming greater relative proportions of total, saturated and trans fats, and less relative proportions of carbohydrates, wholegrains, fiber, insoluble fiber, starch, and resistant starch. Our findings position the CF diet as a potential modulator in gastrointestinal inflammation and the proposed gut-lung axial relationship in CF. The dietary intake of wholegrains, fiber and resistant starch may be protective against intestinal inflammation and should be explored as potential therapeutic adjuvants for children with CF.

Trial registration: ClinicalTrials.gov NCT04071314.

Keywords: Nutrition; akkermansia; cystic fibrosis; gut-lung axis; microbiome.

Figure 1.

Significant differences in macro- and micronutrient intake between CF (n = 19) (red) and HC (n = 19) (blue) groups. Values are adjusted for total energy intake. Shaded regions represent 95% confidence intervals constructed from generalized linear models controlling for age; solid line represents mean.

Figure 2.

Bacterial alpha and beta diversity for stool (CF n = 33, HC n = 33) and airway samples (CF n = 41, HC n = 41). Richness was determined by number of zOTUs (a) and Shannon diversity index (b). Shaded regions represent 95% confidence intervals constructed from generalized linear models controlling for age; solid line represents mean. Beta diversity was calculated with Bray-Curtis dissimilarity to generate non-metric multidimensional scaling (NMDS) plots based on relative abundances (e) and presence/absence data (f).

Figure 3.

Diagrammatic representation of spearman correlations in the multisystem context of cystic fibrosis. (s) = stool genera; (a) = airway genera; FEV₁% = percentage predicted forced expiratory volume over one second; CFPE = CF pulmonary exacerbations in the last three years. Blue line = negative correlation, red line = positive correlation, purple line = both positive and negative correlations.