Bacteria isolated from lung as biotherapeutics in asthma.

International audience

English. Health is mainly influenced by the constant and dynamic crosstalk installed between microbiota and host. This paradigm is especially sustained by the symbiosis existing between intestinal microbes and the gut; similar considerations are currently underway concerning the endogenous microbes of the lungs1. In healthy humans, the lung microbiota is shaped by continual waves of intrusion and expulsion, and the proper establishment of bacterial communities after birth may determine the susceptibility towards respiratory pathologies like asthma. We postulate that the equilibrium of microbes arriving in lungs just after birth may change the onset of asthma. Methods: Primo-colonizing strains were isolated from neonatal lungs of mice. These strains were screened for their immune-regulatory properties after being co-incubated with axenic lung slices or with BEAS-2B human bronchial epithelial cell line. The effect of selected strains towards HDM (House Dust Mite)-induced allergic asthma was tested in mice. Results: Viable bacteria (Staphylococcus, Streptococcus, Enterococcus, Listeria, Lactobacillus, Escherichia coli, Proteus mirabilis) were isolated from the lungs of mice 3 days after birth. One of strains (CNCM I 4969, Enterococcus faecalis) decreased the basal level of TSLP after co-culture with slices of germ-free lungs and decreased the release of inflammatory cytokines in BEAS-2B stimulated by TNF. CNCM I 4969 displayed also protective effects against HDM-induced asthma in young mice.Conclusion: We confirm that appropriate bacterial lung stimuli during early life are critical for susceptibility to allergic asthma2. We also designed a functional and efficient framework to screen lung microbes that could be used as prophylactic or therapeutic applications in respiratory health.