Oral and Environmental Microbiome, Endotoxin and Lung Health; the United Airways concept extended

Dental health may influence disease risk or exacerbate inflammatory conditions in organs at distant sites. The association can be explained by transfer of oral bacteria directly to other organs such as the lungs, or by transport of inflammatory mediators in the bloodstream. In this project we will investigate whether bacteria from the oral cavity and in the indoor environment affect lung health over time. We have analyzed and characterized oral bacteria and 1200 dust samples from the homes of two population-based European lung health studies (RHINESSA and ECRHS) with participants from Northern Europe. The participants are now being followed up with lung function measurements and data on disease status. We will investigate the relative abundance of bacteria that stimulate the immune system's inflammatory reaction. These are mainly endotoxin-producing bacteria, with lipid A as the component that is responsible for inducing inflammation. We have now characterized how these bacteria are distributed in samples from the oral cavity and from the home environment. We see some interesting differences in samples from Norther European homes, with Bergen and Uppsala showing much lower diversity compared to Tartu and Aarhus. We are performing clinical follow-up and interviews and will be able to investigate if the bacterial composition in samples collected at baseline, influence lung health at follow-up. We are also testing dust samples from various home environments in animal models to explore if particular composition of bacteria and microorganisms in the home environment affects lung function and asthma. Further, we have described the types of oral bacteria that are associated with low lung function and lung inflammation. We confirm that the importance of good dental hygiene and good dental health are associated with bacterial diversity in the oral cavity that may also enter the lungs. 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. User involvement will be important for designing strategies for promoting dental health, such as increased awareness and subsidization of dental care for low income groups, which again will reduce social health inequalities. In a public health perspective, improving oral hygiene may become a feasible target for intervention programs aimed at improving lung health and preventing respiratory disease, and possibly also other chronic diseases.

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Poor oral health may affect respiratory disease. The oral cavity is united with the airways, and it is therefore likely that oral bacteria play a role for the association between oral and lung health. The bacterial community of patients with periodontitis is dominated by gram-negative bacteria and a higher lipopolysaccharide (LPS) activity than the healthy microbiota. There are different forms of LPS that vary in inflammatory potency. Bacteria with especially potent pro-inflammatory LPS have been shown to be more common in lungs of asthmatic than in the lungs of healthy individuals. Bioinformatic tools make it possible to cluster bacteria into bacteria with LPS with strong inflammatory effects and others with low- or inhibitory effects. The primary objective of this project is to study how bacterial composition and types of LPS producing bacteria in oral and environmental samples affect lung function and respiratory disease over time. We will use data from two existing population-based lung health studies with prolonged follow-up. As a translation aspect we will complement the associations observed in the epidemiological studies with experimental studies where the different LPS-forms will be tested. If we can identify a causal relationship between oral microbiome and lung health, improving oral health may become a feasible target for intervention programs aimed at improving lung health and preventing future respiratory disease. The decline in use of dental care services is evident among individuals of low social status, and inequalities in oral health are associated with social conditions among elderly in Norway. Consequently, the implementation of the results of this project – where user involvement will have an essential role - has huge potential to reduce social inequalities in health. The overall public health impact is improved quality of life and prolonged life expectancy by improving lung health and preventing respiratory disease.