Descrizione del progetto
Studiare il modo in cui i batteri orali condizionano la salute respiratoria
Poiché la cavità orale è l’ingresso alle basse vie respiratorie, i batteri orali potrebbero svolgere un ruolo nella salute dei polmoni. Batteri con potenti lipopolisaccaridi (LPS) pro-infiammatori sembrano essere più comuni nei polmoni di individui asmatici che di quelli in salute. Il progetto BRuSH, finanziato dall’UE, testerà l’ipotesi secondo cui le comunità microbiomiche dominate da batteri che producono LPS, che inducono una risposta immune pro-infiammatoria particolarmente forte nell’ospite, condizionino negativamente la salute respiratoria. Esso determinerà se una composizione batterica specifica e i tipi di batteri che producono LPS in campioni orali e di polvere predicano la funzione polmonare e la salute respiratoria nel tempo, nonché se i diversi tipi di batteri che producono LPS condizionino gli LPS nella saliva e nella polvere. Il progetto aprirà la strada a una migliore salute orale.
Obiettivo
The oral cavity is the gateway to the lower respiratory tract, and oral bacteria are likely to play a role in lung health. This may be the case for pathogens as well as commensal bacteria and the balance between species. The oral bacterial community of patients with periodontitis is dominated by gram-negative bacteria and a higher lipopolysaccharide (LPS) activity than in healthy microbiota. Furthermore, bacteria with especially potent pro-inflammatory LPS have been shown to be more common in the lungs of asthmatic than in healthy individuals. The working hypothesis of BRuSH is that microbiome communities dominated by LPS-producing bacteria which induce a particularly strong pro-inflammatory immune response in the host, will have a negative effect on respiratory health. I will test this hypothesis in two longitudinally designed population-based lung health studies. I aim to identify whether specific bacterial composition and types of LPS producing bacteria in oral and dust samples predict lung function and respiratory health over time; and if the different types of LPS-producing bacteria affect LPS in saliva saliva and dust. BRuSH will apply functional genome annotation that can assign biological significance to raw bacterial DNA sequences. With this bioinformatics tool I will cluster microbiome data into various LPS-producers: bacteria with LPS with strong inflammatory effects and others with weak- or antagonistic effects. The epidemiological studies will be supported by mice-models of asthma and cell assays of human bronchial epithelial cells, by exposing mice and bronchial cells to chemically synthesized Lipid A (the component that drive the LPS-induced immune responses) of various potency. The goal of BRuSH is to prove a causal relationship between oral microbiome and lung health, and gain knowledge that will enable us to make oral health a feasible target for intervention programs aimed at optimizing lung health and preventing respiratory disease.
Campo scientifico
- medical and health sciencesclinical medicinepneumologyasthma
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health sciencesbasic medicineimmunology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health scienceshealth sciencesinfectious diseasesRNA virusescoronaviruses
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
5020 Bergen
Norvegia