Cystic fibrosis (CF) is a life-limiting autosomal recessive multisystem disease. While its burden of morbidity and mortality is classically associated with pulmonary disease, CF also profoundly affects the gastrointestinal (GI) tract. Chronic low-grade inflammation and alterations to the gut microbiota are hallmarks of the CF intestine. The etiology of these manifestations is likely multifactorial, resulting from cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, a high-fat CF diet, and the use of antibiotics. There may also be a bidirectional pathophysiological link between intestinal inflammation and changes to the gut microbiome. Additionally, a growing body of evidence suggests that these GI manifestations may have significant clinical associations with growth and nutrition, quality of life, and respiratory function in CF. As such, the potential utility of GI therapies and long-term GI outcomes are areas of interest in CF. Further research involving microbial modulation and multi-omics techniques may reveal novel insights. This article provides an overview of the current evidence, pathophysiology, and future research and therapeutic considerations pertaining to intestinal inflammation and alterations in the gut microbiota in CF.

Cystic fibrosis (CF) is a common disorder of autosomal recessive inheritance, that once conferred a life expectancy of only a few months. Over recent years, significant advances have been made to CF therapeutic approaches, changing the face of the disease, and facilitating the partial restoration of pancreatic function. This mini review summarizes the current landscape of exocrine pancreatic management in CF and explores areas for future direction and development.

IntroductionChronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the ‘Evaluating theAlimentary andRespiratoryTracts inHealth and disease’ (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions.Methods and analysisThe EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor.Ethics and disseminationEthics approval: Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals.Trial registration numberNCT04071314

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.

Objectives: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. Methods: This cross-sectional cohort study recruited children with EA and HC aged 2–17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. Results: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. Conclusions: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.