Diet and exercise interventions fail to affect microbiome in CF study

Microbial population in lung and gut stay the same despite therapy

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Neither exercise nor nutritional interventions were found to affect the microbial population — typically an underlying cause of lung function decline and disease progression in cystic fibrosis (CF) — in the lung and gut of people with CF, a study in Germany shows.

That microbial population remained stable despite efforts to improve patient nutrition and exercise.

“In summary, there is a lack of effective microbiome-modulating therapies to overcome the vigorous pathogen [disease-causing]-dominated signature of the CF respiratory microbiome,” the researchers concluded.

The team added that “further studies are required to understand which therapy could destabilize the dominant disease-associated microbial composition of [people with] CF.”

The study, “Resilience and stability of the CF- intestinal and respiratory microbiome during nutritional and exercise intervention,” was published in the journal BMC Microbiology.

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CF is characterized by the accumulation of sticky and thick mucus, particularly in the lungs, gastrointestinal and reproductive organs. It is caused by mutations in the CFTR gene, which provides instructions to produce the CFTR protein that regulates water and salt flow in and out of cells.

In the lungs, the accumulation of mucus promotes the growth of disease-causing microbes. A decreased microbe diversity together with an increased dominance of disease-causing microbes correlate with a decline in lung function and disease progression.

Also, changes in the gut microbiome, the microbial population, are associated with lung infections.

Both diet and exercise may impact microbial composition in CF. For instance, a diet high in fiber or fermented foods might influence immune responses. In people with CF, taking probiotics — supplements with live microorganisms intended to have health benefits in the body — has been associated with fewer pulmonary exacerbations, or sudden worsening of respiratory symptoms. These supplements also may decrease gastrointestinal inflammation. However, the evidence is limited.

Multiple studies also have linked physical exercise with the modulation of the gut microbiome. But any potential impact on the lung microbiome has not yet been studied.

Now, a team of researchers in Germany sought to test whether increased physical activity, nutritional improvements, and supplementation with probiotics could impact the intestinal and lung microbiome in people with CF.

To that end, a personalized diet and exercise program was offered to 18 patients with CF for one year (12 months). Among the participants, 10 (56%) were men, and the median age was 29.5. All but one patient (17 in total) had pancreatic insufficiency, and 14 had a F508del mutation in at least one CFTR gene copy. Pancreatic insufficiency occurs when the body does not make enough of a specific enzyme needed to digest food in the small intestine. The F508del mutation is the most common in CF.

Clinical assessments and microbiome evaluation were performed before the study started, after three months, and after one year.

During the study, participants increased their training minutes per week by 42%. Their strength and endurance training was monitored by a sports scientist via the internet.

Results showed that fat-free mass increased with training. Cardiopulmonary fitness remained stable and lung function decreased.

Nutritional interventions, in the form of counseling, were offered based on food-weighting protocols. Fat and protein intake was 51% and 28%, respectively, and was not altered throughout the study. For CF patients, nutritional recommendations suggest fat intake representing 35%-45% of total caloric intake and protein intake of more than 20%.

All participants took probiotics — specifically Lactobacillus rhamnosus LGG — between months three and 12.

The researchers analyzed stool and sputum samples to assess the impact of the nutritional and exercise interventions on the gut and lung microbiome. Parameters such as microbial diversity, richness and dominance were analyzed.

No differences in diversity were observed over time, indicating a stable microbiome composition, according to the team.

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Microbiome composition was highly specific for each patient and was impacted by disease severity. CF severity explained 8% of the variance in sputum microbiome and 7% of that in stool.

Disease-associated microbes dominated sputum composition. The dominance of Pseudomonas bacteria was linked to moderate-severe lung disease, whereas both Staphylococcus and Streptococcus were dominant in the lung microbiome of individuals with better lung function.

For the lung microbiome, neither training nor lung function parameters were related to changes in microbiome composition. In the gut microbiome, lung function, but not training frequency or time, was significantly associated with microbial changes.

According to the researchers, this suggests “stability and lower-complexity of sputum compared to stool.”

There is a lack of effective microbiome-modulating therapies to overcome the vigorous pathogen [disease-causing]-dominated signature of the CF respiratory microbiome.

Recent antibiotic treatment, either orally or into-the-vein (intravenously), taken within the prior two weeks before sampling, significantly decreased the diversity and richness of the gut microbiome. However, long-term antibiotic treatment burden had a minor influence.

Although not statistically significant, changes in total antibiotic burden explained around 10% of the microbial composition in stool samples, but just around 1% among sputum samples.

“Despite the exercise and nutritional intervention, respiratory and intestinal microbiomes proved to be resilient,” the researchers wrote. Resilience is the ability of the microbiome to remain or return to a stable state composition, demonstrated here by the lack of significant variation in the same patient or between patients.

“We demonstrate that the resilience of the CF respiratory microbiome is driven by the high stability and dominance of disease-associated pathogens,” they added.

The team noted that new, highly effective CFTR-modulator therapies have recently been approved.

These “CFTR-modulator therapeutics might have the potential to surpass the demonstrated resilience of CF microbiomes. Future studies on CF microbiome composition under these therapeutics are needed,” the researchers concluded.

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