Study finds link between low fungi diversity and severity of ARDS

A new study in people with acute respiratory distress syndrome (ARDS) has found a link between a low diversity of fungi in their lungs and their likelihood of developing severe disease.

New research has found that the inflammatory cascade associated with ARDS is linked to a low diversity of fungi in a person’s lungs.

The findings, which the scientists are due to present at the virtual European Respiratory Society International Congress, contribute to burgeoning research on the microbiome. They may also be valuable for better understanding some of the effects of COVID-19.

What is ARDS?

According to the American Lung Association, ARDS is a type of lung injury wherein fluid is able to build up in a person’s lungs, restricting the amount of oxygen they can receive into their blood.

As blood oxygen levels decrease, it can damage vital organs and force them to shut down. This is life threatening. COVID-19, the disease at the heart of the current global pandemic, has been a prominent recent cause of ARDS.

Although the methods of treating ARDS have been improving, interventions still primarily aim to support the person, such as through mechanical ventilation of their lungs.

However, in the new research, the scientists identified a link between the severity of ARDS and the diversity of fungi in the person’s lungs.

This finding may open the door to future interventions that can do more than simply support the person with ARDS.

Lung microbiome

The microbiome comprises all the genetic material within the microbiota. This is the ecosystem of trillions of microbial cells that exist on and within a person’s body. People often associate the microbiome with the gut, and a lot of research has explored the gut-brain axis.

This research connects the health and functioning of a person’s gut microbiome with the health and functioning of their brain, meaning that interventions in one may affect illnesses in the other.

Although the microbiome consists of both bacteria and fungi, bacteria have typically “stolen the show” in terms of research. However, when it comes to the microbiome in a person’s lungs, fungi may also be important.

As study co-author Noel Britton, a Ph.D. candidate at the University of Pittsburgh in Pennsylvania, points out, “In terms of numbers of cells, fungi are outnumbered by bacteria by several orders of magnitude.”

“Additionally, while it is now well-established that the lungs play host to a distinct and dynamic microbiome, they don’t represent a rich environment for microbes to thrive, and they generally have many fewer microbes than the gut — the body site where scientists have focused the most microbiome research.”

“It can be difficult to pick up a signal from such a low mass of fungi and to be sure that the sequences identified are not due to contamination in the laboratory,” she adds.

However, the difficulties associated with assessing the fungi within the microbiome of a person’s lungs could mean that scientists are missing some interesting relationships between the lungs’ fungal microbiome and lung conditions.

As Britton notes, “We wanted to carry out this research as [ARDS] is characterized by a hyperinflammatory overreaction of the immune system, and we know that fungi can be involved in activating and regulating the human immune system.”

“There are no known therapies for the successful treatment of ARDS, and very little is known about why some patients have a hyperinflammatory response. The diversity of the microbiome, and specifically of fungi, may play an important role in understanding why some patients develop ARDS and some do not.”

– Noel Britton

Next-generation sequencing

Between 2011 and 2019, Britton and colleagues enlisted into their study 202 mechanically ventilated patients with and at risk of ARDS.

Of these patients, 21% received a diagnosis of ARDS. Around 61% of the patients were women, and the average age was 50 years.

To analyze the lung fungi, the researchers took mucus samples from the trachea, which leads directly to the lungs, within 48 hours of intubation. The team then analyzed the DNA of these samples using next-generation sequencing.

Fungi diversity linked to severity

The researchers found that the patients with ARDS had a lower diversity of fungi in their lungs than the patients without ARDS.

Furthermore, organ failure, shock, and sepsis were all associated with a lower diversity of lung fungi among the patients with ARDS.

In general, a lower diversity of lung fungi was linked to worse lung injury and a greater amount of the protein pentraxin-3, which is a sign of inflammation.

For Britton, “the association of lower fungal diversity with clinical markers of disease severity is an important finding because it provides evidence for a relationship between the lung microbiome and clinical outcomes in critical illness.”

“We will continue to investigate this further because there is much that is not understood about the development and treatment of ARDS, and this study may point us toward an important diagnostic or treatment-based discovery.”

– Noel Britton

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