Study: Bacteria in Lung in Sarcoidosis Different From Healthy People
Findings suggest alterations may add to abnormal immune responses
The pulmonary microbiota — the collection of bacteria, fungi, and other microorganisms that live inside the lung in people — is less diverse in individuals with stable sarcoidosis than in their healthy peers, a new study suggests.
Notably, this imbalance was more pronounced for fungi than for bacteria. In addition, sarcoidosis patients also showed significantly lower levels of anti-microbial molecules.
These findings suggest that alterations in the pulmonary microbiota may contribute to the abnormal immune responses that cause sarcoidosis, the researchers noted.
The study, “The lower airways microbiota and antimicrobial peptides indicate dysbiosis in sarcoidosis,” was published in Microbiome.
Examining bacteria, fungi in the lung
Sarcoidosis is a highly variable inflammatory disease that can lead to the formation of small clumps of immune cells, called granulomas, in virtually any organ in the body, but most commonly in the lungs.
The disease is thought to be caused by a combination of genetic and environmental factors. Further, it’s hypothesized that infectious agents are contributing factors.
However, “no single candidate has been discovered as the main microbial trigger for sarcoidosis,” the researchers wrote.
The human body is home to billions of bacteria and other microorganisms, which affect health and disease in many ways that are only beginning to be comprehended. The role of the pulmonary microbiome and its imbalance, or dysbiosis, in sarcoidosis remains unclear.
Now, a team of researchers in Norway, the Netherlands, and Spain set out to investigate whether the fungal and bacterial pulmonary microbiota was different between sarcoidosis patients and healthy people. They also assessed whether there was a link between the pulmonary microbiota and anti-microbial molecules.
This study demonstrated that stable sarcoidosis patients have a different fungal and bacterial microbial composition in the lower airways … compared with healthy [people]
Their study included 35 sarcoidosis patients and 35 healthy people, who served as controls. All were participating in The Microbiome in Interstitial Lung Disease study and The Bergen Chronic Obstructive Pulmonary Disease Microbiome study — both focusing on bacteria and fungi in the lung.
Samples were collected from participants’ mouths (the upper airway/oral cavity) as well as from deeper in the lungs.
The sarcoidosis patients were significantly younger than the healthy controls (55.3 vs. 66.3 years) and were more likely to have never smoked (48% vs. 11%). The patients also had a significantly higher proportion of a type of white blood cell called lymphocyte (22.2% vs 12.1%).
Results showed some marked differences in the pulmonary microbiome between the two groups. In one example, sarcoidosis lungs had higher frequencies of fungi of the Eurotiomycetes class, of which Aspergillus, a type of fungi, was the most frequent — but was not detected in samples from healthy people.
In turn, fungi of the Candida group were “significantly less abundant” in lung samples from people with sarcoidosis than in those without the disease, the researchers wrote.
Notably, higher levels of anti-fungal antibodies have been previously found in lung fluid and blood of sarcoidosis patients relative to healthy people, “indicating that fungal infection can be a possible [causative] agent of sarcoidosis,” they added.
There also were significant group differences in terms of the proportion of certain bacterial groups. But the differences in pulmonary microbiota makeup between sarcoidosis patients and controls were generally “more striking” for fungi than were bacteria, the team wrote.
Statistical tests measuring the overall fungal and bacterial diversity in the pulmonary microbiota generally indicated less diversity among sarcoidosis patients compared with healthy controls, with most results reaching statistical significance.
The researchers also noted that the lung levels of certain anti-microbial peptides — proteins made by the immune system to help fight off infections — were significantly lower in sarcoidosis group compared with the healthy group. However, levels of these proteins showed no clear association with microbial diversity.
“This study demonstrated that stable sarcoidosis patients have a different fungal and bacterial microbial composition in the lower airways and oral cavity compared with healthy controls, being most pronounced for fungi,” the researchers wrote.
“Differences between sarcoidosis and controls were found when examining differential abundances of [groups] and differences in microbial diversity,” the team wrote, adding that these findings suggest “the presence of a microbial dysbiosis in the airways in sarcoidosis.”
The team suggested that their findings may shed new light on the causes of the inflammatory disease.
“Low levels of antimicrobial peptides in the airways could be a pathogenic [disease-causing] factor, or a sign of an overwhelmed innate immune response,” the researchers wrote.
“The persistence of granuloma and inflammation in sarcoidosis” suggest that the presence of immune system-triggering factors may contribute to the disease process, “and our study indicates that the fungal microbiota may be part of this process,” they added.
The team stressed that their study was limited by its small size and by the demographic differences between the two groups, among other variables.
“Future research should address whether this dysbiosis has a [disease-causing] role, and thus be a potential target for new treatment principles,” the researchers concluded.