New study challenges long-held view of common bacterial resident of the lungs

Our bodies are teeming with more than 35 trillion bacteria, coexisting in microbiomes inside our guts, mouths, lungs, skin and urogenital tract.

While it's now clear these microbes are associated with health and disease, scientists have only begun to uncover the full scale of their biology and functions.

In a striking example of just how much is still unknown, a new University of Michigan study overturns a 100-year-old assumption about one common bacterial resident of the lungs, Prevotella melaninogenica.

The lab led by Ariangela Kozik, Ph.D., Assistant Professor of Internal Medicine at U-M Medical School and Assistant Professor of Molecular, Cellular and Developmental Biology at U-M, is interested in Prevotella because the bacteria are commonly found in the respiratory tract and reportedly associated with all manner of chronic conditions, yet also found in healthy people. It's also widely thought to be an obligate anaerobe, incapable of surviving in the presence of oxygen.

What, they wondered, is it doing in the lungs?

Kozik, an asthma researcher, notes that Prevotella are found differing amounts inside the respiratory tract in both healthy people and in people with asthma and COPD, accounting for roughly 10% of microbial populations in healthy lungs and up to 13% on average, in individuals with respiratory disease.

To unravel this paradox, Kozik's team subjected cultures of P. melaninogenica to increasing percentages of oxygen, comparing the rates of growth and survival.

They found that the upper threshold for growth was between 5-8% oxygen, and the bacteria could briefly survive oxygen levels as high as 21%.

Furthermore, the study found, using a new real-time sensor platform and RNA sequencing, that Prevotella appear to be consuming oxygen and dealing with oxidative stress and DNA damage differently than other aerobic bacteria.

Prevotella has all of these mechanisms to allow it to survive in oxygenated environments that previously were not appreciated for this organism at all, changing what we thought we knew."

Ariangela Kozik, Ph.D., Assistant Professor of Internal Medicine, U-M Medical School and Assistant Professor of Molecular, Cellular and Developmental Biology, U-M

The ability to exist in the presence of oxygen may lie along a spectrum and not be as clear cut as scientists have traditionally defined, she notes.

Kozik and her lab hope to next interrogate how the immune system responds to Prevotella and dive deeper into lung bacteriology to understand specifically how these microbes affect the body.

"We need to work to look at the bacterial community and ask, how does this community function currently? What metabolites are they making, what signals are they sending to the immune system? How's the immune system responding to it? How does this activity differ in health versus in the context of chronic lung diseases?" said Kozik.

This deeper understanding of the body's various microbiomes could help drive more targeted therapies, she adds.

"Those kinds of questions about the relationships between bacteria and the body are what is a big black box right now."