The oral cavity is the gateway to the lower respiratory tract, and oral bacteria have an important part to play for 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 LPSproducing bacteria which induce a particularly strong pro-inflammatory immune response in the host, will have a negative effect on respiratory health. The hypothesis will be tested in two longitudinally designed population-based lung health studies. BRuSH 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 and dust. BRuSH will apply functional genome annotation that can assign biological significance to raw bacterial DNA sequences. With this bioinformatics tool we 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 2010 Global Burden of Disease has estimated that 3.9 billon people worldwide have poor dental health. According to the WHO, 300 million people have asthma. The prevalence of COPD and asthma is expected to increase because of increasing life expectancy and an aging population. Both periodontal diseases and chronic lung diseases will increase in the coming years due to increasing life expectancy and an aging population. Both disease conditions occur more often in groups with low socio-economic status, and lead to poorer quality of life for those affected. Periodontitis are the most common cause of lost teeth during the lifetime. Symptoms of periodontitis could be bleeding when brushing teeth and during dental flossing, redness, and edema of the gums. Periodontitis are heritable but are also affected by age and lifestyle. Early diagnostics and treatment are important to prevent the disease from developing into more severe forms. The decline in use of dental care is most pronounced among individuals of low social status, and social inequalities in dental health and use of dental care services are evident among elderly in Norway as well as in other European countries. 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.
The objective of BRuSH is first to explore whether the relative abundance of hexa-, penta-, and tetra-acylated LPS-producing bacteria in gingival and dust samples are associated with asthma severity, changes in lung function and respiratory diseases status over time. Secondly, to investigate whether the levels of LPS in oral and dust samples are associated with those outcomes; and whether the contribution of hexa-, penta-, and tetra-acylated LPS-producing bacteria influences these LPS levels. Third, to apply synthetized lipid As in mice models of experimental asthma and in vitro models of human bronchial epithelial cells. To reach these goals, BRuSH will use data and biobank material from two large population-based studies; the RHINESSA generation study (Respiratory Health In Northern Europe, Spain and Australia; www.RHINESSA.net) and the ECRHS study (European Community Respiratory Health Survey; www.ecrhs.org) and in addition in vitro and in vivo models to test how different lipid As influence lung health.
