Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
The lower airways microbiota and antimicrobial peptides indicate dysbiosis in sarcoidosis
We previously published about this research in a story titled “People with Sarcoidosis Have Less Diverse Pulmonary Microbiota Than Healthy Individuals” which can be found here. The study was originally published in the research journal Microbiome. You can read the full text of the study here.
In the rare disease sarcoidosis, the role of the microbiome in the lungs, also called the pulmonary microbiota, isn’t well understood. In this study, an international team of researchers sought to study the pulmonary microbiota in people living with sarcoidosis and compare it to that of healthy controls. Furthermore, they hoped to determine if there was any correlation between the microbiota and the level of antimicrobial peptides (AMPs) found in a region called the protected bronchoalveolar lavage (PBAL).
The researchers looked at data from 35 sarcoidosis patients and 35 healthy controls. These individuals were already participating in other studies that were focused on the effects of fungi and bacteria in the lungs. The sarcoidosis group was younger than the control group and was more likely to have never smoked. The researchers also found that the patients had noticeably higher levels of lymphocytes (a form of white blood cell) in comparison to the controls.
The data revealed significant differences in the pulmonary microbiota of the two groups. Sarcoidosis patients displayed a high prevalence of Aspergillus fungi, which was not found in the healthy controls. Meanwhile, Candida fungi were less abundant in patients and more common in the controls. The scientists commented that prior studies had found higher levels of anti-fungal antibodies in the lungs and blood of sarcoidosis patients.
The research team also noted differences in bacterial composition between the two groups as well. However, the differences in fungi were far notable and important. When put under statistical analysis, the scientists found that the overall diversity of the pulmonary microbiota in sarcoidosis patients was noticeably lessened in comparison to the controls. Patients also had lower levels of AMPs, which are proteins that play a role in the immune system function. However, the team found no association between these levels and microbiota diversity.
Overall, the researchers concluded that these findings could have implications for the origin of sarcoidosis. They also identified the presence of microbial dysbiosis, meaning an imbalance. The team also speculated that the changes in fungal composition and low level of AMPs could play a critical role in the cause of the disease.
The team noted certain weaknesses of the study, such as age differences between the controls and patients, as well as the overall small sample size.
Sarcoidosis is a rare disease which is characterized by the appearance of unusual aggregates of inflammatory cells. These aggregates are called granulomas. The disease can affect almost any part of the body, but it most commonly appears in the lungs, lymph nodes, and skin. Unfortunately, the precise cause of sarcoidosis remains a mystery. The prevailing theory is that it is the result of alterations to the immune response following exposure to a certain trigger, such as an infectious pathogen. Certain genetic mutations, affecting BTLN2 and possibly HLA-DR, are considered risk factors. Sarcoidosis is also associated with certain autoimmune diseases. Symptoms vary depending on the organs affected but may include weight loss, fatigue, bone pain, cough, wheezing, shortness of breath, chest pain, skin ulcers and lumps, and skin discoloration. Symptoms are mild in most cases and many patients can control their disease with ibuprofen. Other treatments for more serious disease include steroids, glucocorticoids, antimetabolites, and immunosuppressants. To learn more about sarcoidosis, click here.
Why Does it Matter?
The results of this study, which indicate that the pulmonary microbiota appears to interact with the immune system, suggest a potential cause or disease mechanism in sarcoidosis that can only be confirmed with further research.
Combined with prior data revealing high levels of anti-fungal antibodies in sarcoidosis patients, the results add further weight to the theory that fungal infection could be at the center of the 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 study authors wrote.
If further research confirms dysbiosis as playing a role in sarcoidosis, it could also serve as a future treatment target.