Matthew Wolfgang was fascinated by two simple truths: people with a specific genetic mutation will get cystic fibrosis (CF), and eventually, a nasty bacterium called Pseudomonas aeruginosa will dominate their lungs. Why that bacterium and not a different but equally bad bug?
“We have no idea,” Wolfgang says. “We all encounter Pseudomonas every day. It’s abundant in soil and on plants. It likes to live in sink taps and shower heads. It doesn’t affect healthy people at all. But as soon as you become immune-compromised it becomes a problem.”
For years, CF researchers thought Pseudomonas was a lone gunman. But now they know that it has accomplices. Wolfgang used UNC’s Microbiome Core Facility to find dozens of bacterial species in the lungs of CF patients. “One is Prevotella,” Wolfgang says. “It normally resides in the mouth and doesn’t really do anything in healthy people. Occasionally it’s associated with abscesses. We’ve been finding Prevotella in high numbers in a lot of our CF patients.”
Wolfgang’s lab also found bacteria that can’t survive in oxygen-rich environments. “This tells you about where the disease has progressed in a patient,” he says. Some CF lungs are so damaged that oxygen can’t reach every part of the lung. Anaerobic bugs infect those areas, causing more inflammation.
Wolfgang says that the antibiotics CF patients take to kill aerobic bacteria are not as effective against anaerobic bacteria. “Maybe patients need combination therapies,” he says. “Maybe those Prevotella bacteria and others play some beneficial role.”
Wolfgang admits it seems crazy to think that any bacteria in the lungs would benefit anyone. Having no bacteria would be best. But a diverse community would be better than one dominated by pathogenic bugs. “It’s like in the gut,” Wolfgang says. “You want a balance. Bacteria fight for space, for nutrients.” You don’t want a really bad bug, such as Pseudomonas, to win that battle.
Wolfgang teamed with researchers in Ireland to study how bacterial communities change over time in CF patients. Turns out that as symptoms worsen and lung function decreases, the bacterial ecology of CF lungs gets less diverse. Pseudomonas becomes more dominant. The correlation is clear, but what to do about it isn’t.
CF patients typically take antibiotics that can have long-term side effects, such as kidney problems. Wolfgang points out that some bacteria in CF lungs are highly resistant to antibiotics. In the end, Pseudomonas dominates and causes major respiratory failure.
Still, trying to keep a CF patient’s lungs bacterially diverse might not be a good idea either. “I’m nowhere near advocating the use of probiotics—colonizing someone’s lungs with bacteria—because we know that the inflammation response to bacteria is doing a lot of damage,” Wolfgang says. “We’re getting a good handle on what’s going on in the lung, but we’re a ways off from figuring out how to intervene in a useful, therapeutic way.”