There is no study to date that has evaluated the impact or effect of a Mediterranean diet in children with CF. The goal of this study would be to help provide better guidance around questions the investigators, as CF care providers continue to receive from patients and families about how to best promote overall health in pediatric cystic fibrosis from a dietary perspective. Currently, the updated nutritional recommendations are variable and broad. Parents continue to search for more concrete guidance about how best to promote long-term health given the ever-increasing life expectancy of cystic fibrosis patients in this new area of advanced therapeutics. Given the changing landscape of the CF care in general, children are less likely to struggle with early life malnutrition, and it is becoming increasingly clear that high fat, high calorie diets are not beneficial nor are necessary for all children with CF.

The dietary needs of children with Cystic Fibrosis continue to change. With the advent of highly effective modulator therapy, these needs are profoundly shifting away from the standard advice of high calorie, high fat to varied, regular and moderated calorie. Obesity is a problem the investigators now confront with regularity and has prompted the need for more specific, dietary advice to parents who are eager to find sustainable meal plans that promote health overall.

There is significant data to suggest that the Mediterranean Diet is the pinnacle of dietary health in everything from metabolic syndrome to ADHD in children. As the investigators look to shift away from the standard approach, the investigators are left to consider how specific dietary intervention may be able to support children with cystic fibrosis. Recent studies suggest Mediterranean diet and those similar were associated with increased abundance of fiber degrading bacteria like Ruminococcus as well as subclinical decreases in fecal calprotectin, a marker of gastrointestinal inflammation. In other inflammatory disease, the Mediterranean diet has also been considered as an adjunctive therapy in mild Crohn's and well as ulcerative colitis disease given its anti-inflammatory properties. Specifically in UC, notable microbiome shifts toward increased production of short chain fatty acids which can have a protective, immunomodulatory role in the gut. Data has shown that the CF gut microbiome is different than it's healthy counterparts and often described as a mix of dysbiosis and low grade chronic inflammation. If the investigators could address the underlying inflammation and dysbiosis in a substantial way with an anti-inflammatory dietary intervention, there is potential to decrease the burden of GI disease and symptomatology that persists despite the widespread use of highly effective modulator therapy.

AIM 1: To test the hypothesis that adherence to a Mediterranean Diet will result in alterations to the gastrointestinal microbiome. The investigators would plan to collect fecal samples for microbiota sequencing before starting a strict Mediterranean diet and then again after completion to assess for specific alterations or signatures in microbial diversity as well as other cytokine or metabolomic alterations. Our translational research core already has infrastructure set up for this process through the Dartmouth Infant and Child CF Cohort Study and many of our families are already familiar with this process.

AIM 2: To test the hypothesis that adherence to a Mediterranean Diet will result in reduction in subclinical markers of gastrointestinal inflammation. Stool calprotectin measurements from samples before and after the study period will allow us to assess for alterations.

AIM 3: To test the hypothesis that adherence to a Mediterranean Diet will result in improvement in gastrointestinal symptoms, the investigators would also employ the PAGY-SYM, which is a widely used gastrointestinal symptom tracker to identify any significant changes in GI symptomatology before and after the anticipated diet window.

AIM 4: To test the hypothesis that adherence to a Mediterranean Diet will result in normalization of anthropometric data the investigators will collect clinical information on subject weight, height, BMI Z score as well as mid upper arm circumference as a way to measure relative nutritional status and fat storage.

Study Endpoints:

Primary: Subjects will adhere to 6 months of exclusive Mediterranean Diet and have post diet intervention analysis of 16s and metagenomic sequencing, cytokine and metabolomic analysis for microbiome assessment.

Secondary: Fecal calprotectin as a marker of intestinal inflammation. Patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) for symptom reporting.

Inclusion Criteria:

• Male and female pediatric patient with cystic fibrosis age 3 and older
• Nutritional status defined as a BMI Z-score of at least -1 or above
• Confirm diagnosis of CF defined by 2 CF causing mutations on genetic testing or sweat chloride greater than 60 mEq/L
• Children with pancreatic insufficient CF and on PERT
• Children with pancreatic sufficient CF not on PERT
• Child must be on a full, solids based diet
• Family willing to child adhere to an exclusive Mediterranean style diet for a period of 6 months
• Child must be able to follow-up at regular CF clinic visits and attend any additional study visits if necessary

Exclusion Criteria:

• Children with malnutrition
• Children who require nutritional supplementation via any type of feeding tube
• Children with poorly controlled CF lung disease
• Children with advanced CF liver disease
• Children with a comorbid gastrointestinal disease such as celiac disease, Crohn's disease or other malabsorptive process to be reviewed by PI
• Children with significant food allergies or other gastrointestinal allergy
• Family is unwilling to adhere to prescribed dietary intervention