What’s the link between bacteria and IPF and how can it unlock new treatments?

Idiopathic pulmonary fibrosis (IPF) is a lung condition which causes the lungs to become damaged and scarred, making it difficult to breathe. The exact cause of IPF is unknown, and we have limited treatment options. It’s a progressive illness which means the scarring gets worse over time. Some treatments can help slow the progress but they don’t work for everyone. There’s currently no treatment that can stop or reverse the scarring.

Professor Phil Molyneux, Asthma + Lung UK Chair of Respiratory Research at Imperial College London, is looking into how bacteria present in the lungs of people with IPF affect how the scarring develops and progresses. And whether targeting these bacteria could lead to more positive outcomes for people with IPF. 

What’s the link between bacteria and IPF?

We think that pulmonary fibrosis is caused by the body responding unusually to what for other people is a normal injury to the lining of the lungs, for example a chest infection or breathing in polluted air. In IPF, something unusual happens and as the body attempts to repair the injury, the wound healing process goes wrong, leading to progressive scarring. My work has shown that people with IPF tend to have more bacteria than healthy people in their airways, even when there’s no infection. The more bacteria there is, the more quickly the condition progresses. But we still don’t understand where these bacteria come from or why they might cause scarring. My idea is that the immune system’s response to these bacteria drives inflammation and scarring in IPF and that by targeting this response, we could improve outcomes for people living with IPF.

How do these bugs get into the lungs of people with IPF?

We don’t know where these bacteria come from so I’ve been looking to see if the bacteria in the gut could be playing a role. We’ve found that patients with IPF have more of a type of bacteria called streptococcus (which is normally found in the lungs) in their stool samples than healthy individuals. It is unclear how the relationship between the gut and lung microbiome evolves so to try and understand the link, we’ve taken samples from the mouth, lungs and stools of the same patients. We’re comparing the bacteria in these samples to see if we can map where the bacteria come from and how they perhaps move between the environments. 

We don’t know if bacteria from the gut move into the lung or if it moves the other way and this work will help us tell that. We think it’s to do with a mechanism called gastroesophageal reflux, which is where stomach acid flows back up into your food pipe and can spill over into the lungs.

What the role of the bacteria is in the progression of scarring in IPF?

We know that the levels of these bacteria in the lungs of patients are associated with worse outcomes. The scarring process in patients with higher levels of bacteria is accelerated and they lose lung function faster. And unfortunately do not survive as long as patients with lower levels of bacteria in their lungs. We are now trying to understand how the bacteria in the gut may cause these worse outcomes.

Acute exacerbations – where people’s symptoms get worse suddenly – can be devastating for people living with IPF but we often don’t know what causes them. We’re looking at changes to the microbiome (the bacteria in the lungs) during and after exacerbations to see if this can give us an insight and potential treatment options.

We’ve been collecting samples from patients when they get an infection or exacerbation. Sampling patients at their baseline and then during any period of decline, will allow me to detect changes in the microbiome before, during and after acute exacerbations.

We now have enough samples to start looking at the impact of these events on patient outcomes and also hopefully understand the triggers of them.

Is targeting lung bacteria is a good way to treat IPF?

We know patients with a higher number of bacteria have a worse survival, so lowering the number of bugs in the airways may be an effective way to treat the disease. Several studies have looked at using antibiotics to treat patients with IPF. But so far none have targeted those specific groups of people with bacterial imbalances in their lungs or looked at the underlying mechanisms.

I’ll be testing antibiotics that people will inhale directly into their lungs to see if they result in a drop in the number of bacteria in the lungs. I’ll also look at why it works better in some people than others, and what this means for those people in terms of how their disease progresses. Then we can hopefully use this to design a clinical trial that can help us develop new ways to treat IPF. 

What does this mean for people with IPF?

My work may uncover new ways to treat IPF, identifying which bacteria to target and which people with IPF might benefit from this treatment. We’ll be able to understand how these bacteria could trigger exacerbations and speed up progression of the disease so we can identify new targets for treatment. This means we can hopefully slow down the scarring and improve the quality of life for people living with IPF so they can live better for longer.

People with IPF are often subjected to invasive and painful tests, like bronchoscopies where a camera is inserted into the lungs through the throat, which can be very distressing. As part of this work, we want to find easier, less invasive ways to assess the bacteria in the lungs which could also be used at home in the future. 

It will generate a completely new understanding of how bacteria can affect the lungs, which will have implications in many diseases, not just IPF.