Analysing cow's milk and big data to prevent asthma

Unprocessed cow's milk appears to prevent asthma in children. Step by step prof.dr. Ben Marsland (Monash University, Australia) uncovers how this works as participant of the Asthma Prevention Consortium. He favours a holistic view on asthma and preventive treatment. 'Asthma is complex. But this provides lots of possibilities too.'

All projects of the Asthma Prevention Consortium revolve around natural products that are strongly suspected of having a preventive effect against asthma. One such product is unprocessed cow's milk. Drinking this in early life appears to prevent the immune system from going in overdrive and causing chronic inflammation of the lungs (asthma). How exactly this works is not yet clear. The research group Marsland leads aims to find out. 'We know that diet, gut, microbes in the body (the microbiome), metabolism and even the nervous system are related to it. We now aim to unravel how.'

Mechanism uncovered
In 2021 Marsland made huge steps forward. In mice studies he found out what 'ingredient' of unprocessed milk protects against asthma: the culture of bacteria that naturally grows in it. In a different study, a group of lab mice displayed a surprisingly strong protection against asthma. Marsland's group investigated this and identified a molecule in the lungs called PCS as the instigator. They also discovered its source: PCS was released by bacteria in the gut of mice while metabolising an amino acid, L-tyrosine. The researchers then put 1 and 1 together and tested if their bacteria, from unprocessed milk, are capable of metabolising L-tyrosine. Marsland: 'And some of them are! Furthermore, such milk contains casein. This peptide is a source of L-tyrosine.'

Now one of the possible protective mechanisms of unprocessed milk is uncovered. 'And a promising starting point for treatment found.' The discovery even made the national news in Australia. In the item Marsland expressed his hope to start clinical trials in 2021 to test an L-tyrosine formulation in humans. This hasn't happened yet. 'We are very eager. But we ran into practical problems. Once the funding of the clinical project comes through, we are set to go.'

Very exciting
Meanwhile Marsland continues other research. He examines the different species of bacteria in unprocessed milk to determine if they all have preventive properties. And whether these work through the PCS-pathway.

Also, Marsland is involved in clinical research of German consortium colleague's prof.dr. Erika von Mutius and prof.dr. Markus Ege. In a group of 150 children they study the effect of drinking unprocessed cow's milk relative to supermarket milk in early age: is the incidence of asthma different? Marsland zooms in on physiological effects. He processes nasal swaps, samples of blood and faeces to measure allergic sensitivity and microbiome composition. 'This is the first clinical study, so it is very exciting. Also, by comparing the results to those in mice, we can check if mice are a realistic model.'

Most of Marsland's research is done in mice. 'This is unavoidable,' he says. Asthma is complex. The immune system is influenced by a lot of factors, like the environment, age, genetic factors, microbiome in the gut and even the skin, brain and the nervous system. 'We need to be able to set, control and measure all factors. Also, it is required to take tissue samples from the lungs. This cannot be done with humans.'

To illustrate the complexity: some children who are at risk of developing skin allergies can cascade towards food allergies and asthma.But this complexity also poses potential solutions, Marsland emphasizes. 'When we understand how factors like gut microbiome, skin and nervous system interact, I expect to find critical junctions of pathways.’ For this, Marsland works with a wide range of scientists and clinicians like neurologists and gastro-endocrinologists.

World of possibilities
‘We can learn to control the pathways in order to treat and prevent asthma and other allergic reactions.  This requires a more holistic view of asthma,’ Marsland says. ‘And you need a lot of data on a lot of people. One great thing about science now, is that scientists share the huge data banks they create during research. This broadens our view and speeds up the scientific process. There is a whole world of possibilities to discover.'

So besides lab work, analysing big data is very important. Marsland: 'In high school I was strong at computers and programming. I went to university to study this, but found it very dull. I switched to biology and was captivated by immunology. Remarkably, now half of my research group are programmers that help organize and analyse the data.

Follow the data
Within this consortium Marsland also gets to follow a wide range of data, which he finds stimulating. And this is not common, Marsland explains. ‘Traditionally, in science you come up with an idea about how something works. And you test this. In this consortium of Lung Foundation, we exchange results from very different projects. This way we stumble upon connections we could never have come up with. I believe this will lead to new possibilities to prevent children from getting asthma.'

Text: Karin Postelmans