Gut-lung Axis Likely in CF, High-fat Diet May Drive Inflammation

Study in children suggests fewer high-energy 'junk' foods support lung health

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Children with cystic fibrosis (CF) show significant differences from healthy children in the quality of their food choices and, subsequently, the microbes in their gut and respiratory tract, with evidence of greater intestinal inflammation in these young patients, a recent study in Australia found.

Certain microbes in the gut associated both with a high-fat diet and CF clinical features, namely lung function, respiratory exacerbations (sudden periods of lung symptom worsening), and body mass index for children beginning at age 10.

“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,” the study’s researchers wrote.

“Our findings position the CF diet as a potential modulator in gastrointestinal inflammation and the proposed gut-lung axial relationship in CF,” they added, suggesting that a diet with fewer saturated and trans fats and more whole grains, fiber, and resistant starch could benefit patients.

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The study, “Diet and the gut-lung axis in cystic fibrosis — direct & indirect links,” was published in the journal Gut Microbes.  

The gut microbiome, a collection of friendly microorganisms (microbes) that populate the gastrointestinal tract, is important for maintaining proper gut function, metabolism, and immune health.

It’s been increasingly recognized that CF patients exhibit gut dysbiosis, or an imbalance in this community of bacteria, fungi, and viruses in the intestinal tract. Such an imbalance can contribute to gut inflammation, among other health problems.

A gut-lung axis has been proposed, in which the intestinal tract and the lungs communicate bidirectionally through microbial and immune interactions. This interaction ultimately can influence the course of diseases impacting the lungs, such as CF.

Diet is one modifiable factor for the gut microbiome. For CF patients, the recommended diet is one high in energy, and it is “commonly being met” by favoring high-fat and nutrient-poor, processed “junk foods,” the study noted.

But research into the multifaceted relationship between the high-energy CF diet, the microbiome, and CF symptoms is lacking. Scientists examined these factors among 41 children with CF and 41 age- and sex-matched healthy children, who served as a control group. The mean age for both groups was around 10 years old.

The study formed part of a larger program called EARTH (NCT04071314), or Evaluating the Alimentary and Respiratory Tracts in Health and disease, conducted at the Sydney Children’s Hospital from April 2018 to September 2019.

All participants provided stool and airway samples — collected via a sputum sample or oropharyngeal swab — for analysis of the microbiome, and dietary intake was evaluated by a dietitian.

Significant differences in diet were found between children with CF and their healthy peers. In line with a recommended CF diet, young patients consumed significantly more energy, but also ate more fats, fewer carbs, starch, whole grains, and fiber. They also took in more iron and magnesium, but less vitamin B12.

The dietary analysis supported the concept that CF children eat a high-energy, albeit nutrient-poor, diet.

Lesser bacterial diversity and richness evident in gut, respiratory tract

Patients also exhibited significant dysbiosis in the gut and respiratory tract compared with healthy children. Particularly, a reduced bacterial richness and lower bacterial diversity in the stool and airways was evident, and they “remained consistently lower throughout life” in these children, the researchers wrote.

Dozens of groups (genera) of bacteria were at altered levels in the stool and airways of CF children relative to controls. They also had elevated levels of calprotectin in the stool, a sign of intestinal inflammation.

Ultimately, higher calprotectin in CF children was significantly associated with a diet heavier in takeout and other “non-core (i.e. junk)” foods. Conversely, lower calprotectin levels associated with eating whole grains, healthy “core” foods, protein, and the nutrients folate, thiamine, and iron.

Subdoligranulum bacteria in the stool were linked to eating more saturated fats, trans fats, and retinol but less fiber, whereas Eubacterium ventriosum associated with eating less whole grains and fiber.

Notably, certain gut microbes also linked to clinical CF features.

For CF children over age 10, at which point lung function deteriorated and pulmonary exacerbations increased, higher levels of Akkermansia bacteria — generally found at lower levels in CF than healthy children — associated with better lung function.

Interestingly, lesser evidence of intestinal inflammation also associated with a greater abundance of Akkermansia in all CF children.

Although Akkermansia bacteria is a known suppressor of inflammation, “the mechanism by which this gastrointestinal organism might influence lung function remains largely unknown,” the researchers wrote.

Pulmonary exacerbations and body mass index also linked to the presence of certain groups of bacteria among children starting at age 10.

Altogether, this study supports the concept of a gut-lung axis and suggests that the adage “you are what you eat” might hold some truth, the researchers noted.

Diet modifications could positively influence the gut microbiome and, in turn, CF symptoms, the team suggested. Still, the researchers noted that “dietary interventions are unlikely to completely restore the [gastrointestinal] or respiratory milieu.”

Its findings, rather, offer a “cross-sectional snapshot,” and long-term studies are needed to evaluate these relationships over time, the team wrote.

“The high fat CF diet warrants a contemporary review in the context of an aging CF population, the greater risk of colorectal cancer (CRC) in young adults with CF and the issues of weight gain associated with cystic fibrosis transmembrane conductance regulator [CFTR] modulator therapies,” the scientists added.

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