In Europe alone, approximately 30 million people suffer from bronchial asthma. In many cases, the disease is manageable, but a complete cure is not yet possible. Asthma is known to be caused by a disrupted immune response in the airways, which leads to a pathological reaction to otherwise harmless agents. The respiratory microbiome is a promising area of research that could contribute to understanding the mechanisms of asthma development and the development of fundamentally new treatments. Studying the bacteria and viruses that inhabit the airways of healthy and sick individuals, as well as their relationship with the body's immune functions, could reveal ways to modulate the microbiome using bacteriophages.

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The CURE project , a multidisciplinary initiative launched in 2017 and part of the EU's Horizon 2020 research program, is being implemented. The project's goal is to use bacteriophages to restore the balance of the respiratory microbiota and thereby normalize immune function in asthma patients. The project involves scientists from Greece, Poland, Georgia, Sweden, the United Kingdom, Switzerland, and European respiratory patient associations.

The idea to study the potential of bacteriophages in asthma treatment arose from the observation that asthmatic patients have fewer phages in their airways than healthy individuals. What role do phages play? Perhaps they help control the numbers of certain bacteria in the airways, or perhaps the absence of phages indicates a lack of bacteria essential for respiratory health. The CURE project was initiated to investigate this.

What was planned?

In the first phase of the project, researchers planned to compare the respiratory microbiomes of asthmatic patients and healthy individuals. In addition to bacteria, these studies would include viruses and virus-bacteria interactions. The next stage involved constructing a model of the respiratory microbial ecosystem and studying the impact of bacteriophages on both it and the host immune system. Next, based on the data obtained, the scientists planned to create a library of bacteriophages that could be useful in the treatment of asthma (this part of the project is being carried out by the George Eliavi Bacteriophage Institute in Georgia). Finally, the plan was to create phage cocktails that would modify the respiratory microbiome of asthmatic patients and alleviate the disease or, ideally, cure it.

What's on for today?

In the spring of 2020, in their latest project report , the authors noted that they had already reached halfway point. They studied respiratory microbiomes and their correlation with asthma symptoms and immune response in 60 asthma patients and 30 healthy volunteers (controls). Respiratory samples were collected from each participant multiple times to monitor the dynamics of microbiome changes.

It turned out that respiratory microbiomes vary significantly between individuals, more so than within a single individual over time, suggesting that the microbiome is "personalized." Dominant microbial families (representing approximately 10-15% of all microbiome species) and their ratios remain stable for each patient. However, asthma patients exhibit greater microbiome variations over time than healthy individuals, for whom the microbiome is relatively stable. This is consistent with the idea that while health is associated with stability, disease can manifest itself in a variety of different states. Monitoring microbiome dynamics in patients allowed the researchers to identify patterns characteristic of asthma exacerbations and their absence.

The project also examined the impact of phages on the respiratory tract, including both the integrity of epithelial cells and local immune responses. Phages were shown to not harm the structure of the mucosa. At the same time, phages activate nonspecific immune cells in the respiratory tract, suggesting a role for phages in the development of immune tolerance.

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A library of phages specific to bacteria considered important in the pathogenesis of asthma is also being developed: representatives of the genera Moraxella, Acinetobacter, Streptococcus, Haemophilus, and Staphylococcus . Thirty new bacteriophages have already been isolated and characterized. An algorithm for describing the network of interactions between bacteria and phages has also been developed, allowing prediction of the bacterial host range of a bacteriophage.

The immediate goal of the project is to create a computer model of changes in the respiratory microbiome in individuals with asthma to predict the impact of bacteriophages.

Currently, in most European countries, bacteriophages are approved for clinical use only in exceptional cases, when other medications are ineffective. However, the project's authors hope that the success of their research will further push for regulatory changes and the widespread approval of phages.

Source: Sacher, J. (2020). Could phages cure asthma? Capsid & Tail, (76).