Link Between Sarcoidosis and Lung Microbes to Be Studied in NIH-Funded Project

A project studying the possible link between sarcoidosis and lung microbes received a four-year, $2.7 million grant from the National Institutes of Health (NIH). The research will be conducted at the University of Illinois at Chicago and may help predict disease prognosis.

Sarcoidosis is an inflammatory disorder that can affect the lungs, lymph nodes, eyes, skin, and in some cases the heart. Research has shown that up to 20 percent of patients with sarcoidosis develop pulmonary fibrosis, which is associated with significant morbidity and can be fatal. Respiratory symptoms commonly observed in sarcoidosis patients include persistent dry cough, fatigue, and shortness of breath.

Although the disease’s course can be short and mild, some patient groups, such as African-Americans, tend to develop long-term and more severe disease. But what causes this difference remains largely unknown.

Similar to the gut, the lung microbiome — which refers to the population of bacteria, viruses, and fungi present in the organ — also plays a role in the disease. Prior studies indicated that an inflammatory response to microbes may cause the development of sarcoidosis, but the identity of these disease-causing agents remains unknown.

“We think that sarcoidosis may be driven by interactions between the host’s lung microbiome and their immune system, rather than by a single organism,” Patricia Finn, co-principal investigator on the grant, said in a press release.

“People who are resilient and don’t develop a severe form of the disease may have different microbiome/immune response signatures compared to those that go on to develop severe sarcoidosis,” Finn added.

Finn’s research team previously reported that the microbiome of patients with sarcoidosis is different from that of healthy individuals. Her work also identified biomarkers associated with disease severity and worse lung function. The investigator also revealed that patients with sarcoidosis have abnormal activation of cell death and autophagy, a cellular process that removes damaged proteins and organelles and is essential for cell survival.

In their new study, the scientists will recruit approximately 170 sarcoidosis patients followed at the Bernie Mac Sarcoidosis Translational Advanced Research (STAR) Clinic and the UIC Center for Lung Health. Researchers will analyze the DNA of microbes collected from lung, blood, and stool samples and assess differences in immune responses to the microbes.

“Two sarcoidosis patients may have very similar lung microbiomes, but in one patient, their disease progresses rapidly, while in another, the disease remains stable,” said David Perkins, co-principal investigator on the grant. “So we want to know if there is a difference in how their immune system responds to the microbiota that might be the factor driving worsening sarcoidosis.”

The investigators will also evaluate whether patients’ microbiome and immune response change over the course of two years.

“We’ll be looking for biomarkers linked with worsening or improving disease over time,” Perkins said. “That way we may be able to predict who will get worse over time and approach the clinical care of that patient with that in mind.”