Oral Primo-Colonizing Bacteria Modulate Inflammation and Gene Expression in Bronchial Epithelial Cells

Abstract

The microbiota of the mouth disperses into the lungs, and both compartments share similar phyla. Considering the importance of the microbiota in the maturation of the immunity and physiology during the first days of life, we hypothesized that primo-colonizing bacteria of the oral cavity may induce immune responses in bronchial epithelial cells. Herein, we have isolated and characterized 57 strains of the buccal cavity of two human newborns. These strains belong to Streptococcus, Staphylococcus, Enterococcus, Rothia and Pantoea genera, with Streptococcus being the most represented. The strains were co-incubated with a bronchial epithelial cell line (BEAS-2B), and we established their impact on a panel of cytokines/chemokines and global changes in gene expression. The Staphylococcus strains, which appeared soon after birth, induced a high production of IL-8, suggesting they can trigger inflammation, whereas the Streptococcus strains were less associated with inflammation pathways. The genera Streptococcus, Enterococcus and Pantoea induced differential profiles of cytokine/chemokine/growth factor and set of genes associated with maturation of morphology. Altogether, our results demonstrate that the microorganisms, primo-colonizing the oral cavity, impact immunity and morphology of the lung epithelial cells, with specific effects depending on the phylogeny of the strains.

An Isolate of Streptococcus mitis Displayed In Vitro Antimicrobial Activity and Deleterious Effect in a Preclinical Model of Lung Infection

“…We have previously isolated bacterial strains from the buccal cavity of human newborns and showed that primo-colonizing bacteria impact the immunity and morphology of the lung epithelial cells, with specific effects depending on the phylogeny of the strains [ 30 ]. From these primo-colonizing strains, we have identified an S. mitis ( S. mitis EM-371) strain that displays interesting promising probiotic capacities ( Table 1 ).…”

“…Furthermore, the S. mitis EM-371 modulated cytokine/chemokine production by the bronchial epithelial cells. This strain modulated the release of some cytokines, chemokines and growth factors (e.g., IL-7, MIF, basic FGF, CCL1, CCL21, CCL25 and CCL26) but did not display a pro-inflammatory cytokine profile [ 30 ]. In addition, in the bacterial culture supernatant, the S. mitis EM-371 produced up to 4.1 mM of acetate, which may modulate the immune system [ 32 ].…”

“…Note that the objective of the present work was not to reconstruct the gene clusters involved in bacteriocin production but rather to get clues on the potential antimicrobial properties of our strain. In a previous study, we showed that S. mitis EM-371 modulates gene expression and cytokine/chemokine/growth factor production in bronchial epithelial cells [ 30 ]. The strain did not display a pro-Th1 inflammatory profile but was able to modulate inflammatory pathways and secretion of immune-related proteins in BEAS-2B cells.…”

“…The S. mitis EM-371 was previously isolated from the oral cavity of a 5-day-old human newborn (as described in [ 30 ]). The strain was cultivated in a brain heart infusion (BHi) (Ref #237500, BD/Difco, Fisher Scientific, Thermo Fisher Scientific, Waltham, MA, USA) broth medium supplemented with 5 g·L −1 of yeast extract (Ref #212750, BD/Difco, Fisher Scientific, Thermo Fisher Scientific, Waltham, MA, USA).…”

“…We have previously isolated an S. mitis strain ( S. mitis EM-371) from the buccal cavity of a human newborn [ 30 ]. The objectives of this study were to (i) investigate the EM-371 strain genome in silico to identify genes potentially conferring antibacterial properties; (ii) validate, in vitro, the growth inhibitory effects of S. mitis EM-371 against multiple strains of H. influenzae , S. aureus and P. aeruginosa species; and (iii) establish whether this strain protects against bacterial infection in vivo in a murine model and, thus, if in vitro testing could predict the in vivo response.…”