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.

KEYWORDS:

• Nutrition
• microbiome
• cystic fibrosis
• gut-lung axis
• akkermansia

Acknowledgments

We gratefully acknowledge the contributions of the individuals and their families who participated in this study. We would also like to thank the contributions of Jessica Halim, Keerti Paida, Jumaana Abdu and the exceptional CF Multidisciplinary Team at Sydney Children’s Hospital Randwick.

Authors contributions

IM was heavily involved in patient recruitment and was a major contributor in designing figures and writing the manuscript. JVD analyzed and interpreted the 16S rRNA, patient, and dietary data and was a major contributor in designing figures and writing the manuscript. CYO and MC conceived and designed the study, contributed to figure design and were heavily involved in editing the manuscript. TT provided study design and methodology support. TK, MD, BP, LO, YB, SC and AJ are responsible for patient care and the collection of clinical data and airway samples at the Cystic Fibrosis Clinic at Sydney Children’s Hospital, Randwick. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical Approval and Consent to participate

Consent was received from all participants according to ethics approval: Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26).

Availability of data and materials

Data presented in this research paper was obtained according to the Evaluating the Alimentary and Respiratory Tracts in Health and Disease (EARTH) Research Program, registered in clinicaltrials.gov (NCT04071314). The datasets generated and analysed for the current study are available in the figshare repository, DOI: 10.6084/m9.figshare.19416830.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2022.2156254

Additional information

Funding

This project was supported by the National Health and Medical Research Council, Australia (NHMRC).