Bacteria isolated from lung as biotherapeutics in asthma

Health is mainly influenced by the constant and dynamic crosstalk installed with microbiota. 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 lungs (Mathieu. E et al, Frontiers in physiol. 2018). The lung microbiota is shaped by continual waves of intrusion and expulsion, and the proper installation 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. 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. 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 (CNCMI4969, E. 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 pre-stimulated by TNFa. CNCMI4969 displayed also protective effects against HDM-induced asthma in young mice. Appropriate bacterial lung stimuli during early life are critical for susceptibility to allergic asthma (Remot. A, et al, 2017, ISME J.). We also designed a functional and efficient framework to screen microbes for applications in respiratory health.