By studying the behavior of microorganisms in the respiratory tract of patients during bacterial pneumonia, the Phenomenon Project hopes to identify bacteria or Probiotics Which will be given to patients to improve their chances of recovery.
Article can be found in Inserm Magazine Issue 60
Despite progress in the management of bacterial pneumonia, about one-third of the 500,000 cases treated annually in hospital end in treatment failure. The introduction of new antibiotics will not be enough to counter this observation, when we know that bacteria will become resistant sooner or later. Therefore, it is a completely different model that must be developed today to better treat these pneumonias. Researchers from the Phenomenon project, created in the summer of 2023, believe the answer lies in the microorganisms in the patient’s respiratory system. ” It has long been thought that the lung is sterile and that pneumonia results from infection with isolated pathogens.“, explains Jean-François Timset, one of its founders. We now know that our respiratory tract is colonized by a community of “symbiont” bacteria, which live in harmony and regulate breathing. Immune response From our airlines. When treating a respiratory infection, local homeostasis is disturbed. Our research will allow us to understand how these disorders lead to therapeutic failure. »
Does the bacteria or antibiotic cause the disappearance of one or more beneficial commensal bacteria of the lung microbiota? Do they disrupt their metabolism? The project will explore these different avenues with two main aims: to identify changes in the composition or function of the respiratory microbiota associated with therapeutic failure, and to find new therapeutic approaches. ” It is a very ambitious project, in an unknown fieldComments by Jean-François Timsit. The difficulty will be to sort through the statistical associations that will emerge between the state of the microorganisms and that of the patient, in order to find those for which there is a cause-and-effect link. »
Bacteria, potential treatments for infections?
under European PAH Project2In Nantes, Antoine Roquely studied the gene expression (microbiome) of respiratory microbes, and showed that a decrease in the abundance of four bacteria was associated with severe pneumonia requiring respiratory assistance. In the context of the phenomenon, he would like to go further: “ Now that we have identified these types, we will examine the metabolic functions they provide and how they fluctuate with the patient’s clinical outcome. » He also wants to repeat the same work to treat less serious pneumonia. To do this, he will use bacterial samples obtained from four groups of patients, which Jean-François Timset and his team are currently conducting in residence in Nantes and Paris. ” Each combines different profiles: mild pneumonia treated on an outpatient basis, community-acquired pneumonia requiring hospitalization, severe community-acquired pneumonia that is admitted to intensive care, and severe nosocomial pneumonia that is admitted to intensive care. . » Samples will be taken from the pharynx and bronchi at the beginning of the disease, during treatment with antibiotics, and in the event of treatment failure. The diversity, richness and function of microorganisms will be analysed, compared to healthy subjects. Moreover, from these samples, gene expression analysis and analysis of small molecules produced by local metabolism will make it possible to determine the functions of the microorganism and, secondly, what functions of the host immune system are modified during infection.
” In the second part, we will validate the results in animals through a more careful study of the bacterial species or metabolic pathways that have been described as interesting. “, explains Antoine Roquely. Ultimately, this work could lead to new therapeutic perspectives: if the disappearance of a type of bacteria turns out to be detrimental to healing, restoring its presence could help fight the infection. The idea of injecting bacteria into the body could become “Patient treatment for pneumonia is a reality.” We can imagine that we will test the respiratory microorganisms of patients while they are hospitalized for pneumonia, before starting antibiotic treatment.Jean-François Timset suggests. Those with a microbiota that is at risk for unfavorable outcomes can receive probiotics, via aerosol or orally. Prophylactic probiotics may also be prescribed to people at risk of pneumonia, such as the elderly, with the aim of stabilizing respiratory microorganisms. »
The resistance: friend and enemy
The good bacteria normally present in the respiratory microbiota of patients can naturally possess antibiotic resistance genes: this feature allows them not to disappear during treatment. But if these resistance genes are transferred to pathogenic bacteria, through a phenomenon called “gene transfer,” the latter will in turn be resistant to antibiotics…” Currently, there is little data on this topic, but the probability of transferring a resistance gene from one bacterium to another is generally higher when the bacteria are structurally close. “, explains Etienne Roby, also a researcher within the unit Insrm Infection, antimicrobials, modeling, evolution. Using samples from different groups, the scientist identifies all the resistance (or resistance) genes to the microbes, and assesses whether the presence of one of them is associated with a lower chance of recovery from pneumonia. In this case, it is necessary to determine the possibility – and the mechanisms – by which genes are transferred from the commensal bacteria to the pathogen. Resistance analysis can therefore lead to the identification of commensal bacteria whose genome is useful for maintaining lung function during the treatment of pneumonia. After identifying resistance genes, Etienne Ruby will synthesize the corresponding proteins to better understand how antibiotics arise and which antibiotics enable them to resist. ” These types can then be used as Probiotic At the time of antibiotic treatmentHe continued. But since the bacteria in the respiratory flora are difficult to isolate and culture outside the lungs, other bacteria that would protect the previous bacteria from the action of the antibiotic and that would be easier to deal with could also be used as probiotics. “Real bodyguards. However, there is another approach, also innovative, when we know that 60% of deaths resulting from infection in France are due to pneumonia.
Jean-François Timset and Etienne Roby are both researchers on unity Infection, antimicrobials, modeling, evolution (IAME, Unit 1137 Inserm/Université Paris-Cité/Université Sorbonne Paris Nord), Paris.
Antoine Roquely co-leads the team Host-pathogen interactions, inflammation and mucosal immunity in the middle Translated research PhD in Organ Transplantation and Immunology (CR2TI, Unit 1064 Inserm / University of Nantes), in Nantes.
Author: C.J.
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