Where are we now in the CURE project?
CURE is now at half way of the project and interesting new findings are cumulating. The annual meeting took place in Syros, Greece, on 15-16 September 2019, where all the partners presented the progress in their work and many more outcomes have arisen since then!
Significant amount of samples have been gathered for biological analyses
The National and Kapodistrian University of Athens (N.K.U.A) and the Medical University of Lodz (MUL), clinical partners of CURE, have followed about 60 patients with asthma as well as 30 healthy individuals in two phases: during the first month, when they tool samples at 8 different time points and, during a whole year, adding another 5 regular samplings. The aim of these two phases is to study if and how the microbiome changes in time and if it correlates with symptoms and/or the immune response.
In addition to regular samples, 32 asthma exacerbations were identified, and samples obtained. These are important because it is expected that major changes of the microbiome may happen during such events, usually caused by a viral infection.
Do phages play a role in regulating the inflammation of asthma?
The Swiss Institute of Allergy and Asthma Research (SIAF) and the Biomedical Research Foundation, Academy of Athens (BRFAA) looked further into tissue integrity and the effect of phages on innate immunity. Using epithelial cells cultures exposed to Staphylococcus phages, they did not find any effect of the phages on the integrity of the tissue or on the molecules that hold the tissue together (‘tight junctions’). Nevertheless, phages were able to change the numbers, activation state and affect differently subgroups of ‘innate lymphoid cells’ (ILCs), suggesting a potential contribution of phages in immune tolerance and inflammation regulation.
Changes in the microbiome are associated with the disease state of asthma
A key question on evaluating the possibility of influencing the microbiome on the airways is linked with how it changes in time. The University of Manchester (UMAN) has sequenced and evaluated samples from different groups of people. In all these groups, the microbiome was more different between patients than within a patient at different times (i.e. the microbiome is 'personalised'). Dominant families of microbes remained relatively stable within each patient; a core microbiome representing 10-15% of species, with a stable proportion among bacteria, fungi, archea and viruses was observed and was often shared between patients. They also observed that asthma patients have more dispersed microbiomes than healthy individuals. This observation supports the idea that while health is organized around a particular state (i.e. it is stable), disease may have many different states. Finally, they have observed, that baseline (steady state) microbiome characteristics can be used to cluster together patients, who had or not an exacerbation. These data further our understanding about the dynamics of the microbial communities in the airway and the opportunities for intervention.
Establishing a well characterised bacteriophage cocktail as a potential treatment for asthma
The Georgi Eliava Institute of Bacteriophagy, Microbiology and Virology (ELIAVA) and the ELIAVA Bio Preparations LTD (ELIBIO) are working intensely to generate a well characterised collection of bacteriophages. These bacteriophages are aimed at targeting bacteria considered important in the upper respiratory microbiome in regard to asthma (Moraxella, Acinetobacter, Streptococcus, Haemophilus and Staphylococcus). A large number of strains from these bacteria have been collected from various sources and used for experiments. At the moment, over 30 new phages have been discovered and characterized.
However, there are so many bacteriophages that we will never be able to isolate them all . For this reason, we need to build computer predictions (‘networks’) of how different phages interact with different bacteria. We developed and tested an algorithm able to describe the phage-bacteria network and saw that there are phages who infect many bacteria and others that are more selective.
We have also started to set up a culture system that will represent the human airway and in which phages and bacteria will interact over human epithelial cells. A prototype of the device to house this culture system has been developed.
Building a prediction model on the impact of bacteriophage interventions in asthma
Finally, the University of Manchester is exploring several approaches for developing mathematical models of how the microbiome changes over time. They adapted some existing programs that could model how a small number of species may interact between themselves, to describe more complex bacterial and viral communities. Currently they are also tweaking a tool designed for large datasets, such as the one that CURE is developing.
“New phages have been identified, we have confirmed and are starting to understand the tolerance of the human immune system towards phages and we have visualised for the first time how the communities of microbes change in time and in relation to asthma activity. The group remains passionately interested and intrigued by the CURE concept. It appears that we will continue having great and satisfactory time in the next two years.” Prof. Nikos Papadopoulos, Coordinator of CURE
 Microbiome: The microorganisms in a particular environment (including the body or a part of the body).
 Epithelial or tissue integrity: The ability of body tissues to regenerate and/or repair to maintain normal physiological process.
 Phage or bacteriophage: Type or virus that infect bacteria.
 There are an estimated 1031 phages on the planet and only 2000-3000 phages have been isolated and studied by now in bacteriophage research.
 Bacterial-phage network or interaction: Phage means ‘bacteria eater’. Phages interact and infect specific bacteria without infecting other types of bacteria. Therefore, there is a constant interaction between both.