Dysbiosis of the gut and lung microbiome has a role in asthma

Abstract

Worldwide 300 million children and adults are affected by asthma. The development of asthma is influenced by environmental and other exogenous factors synergizing with genetic predisposition, and shaping the lung microbiome especially during birth and in very early life. The healthy lung microbial composition is characterized by a prevalence of bacteria belonging to the phyla Bacteroidetes, Actinobacteria, and Firmicutes. However, viral respiratory infections are associated with an abundance of Proteobacteria with genera Haemophilus and Moraxella in young children and adult asthmatics. This dysbiosis supports the activation of inflammatory pathways and contributes to bronchoconstriction and bronchial hyperresponsiveness. Exogenous factors can affect the natural lung microbiota composition positively (farming environment) or negatively (allergens, air pollutants). It is evident that also gut microbiota dysbiosis has a high influence on asthma pathogenesis. Antibiotics, antiulcer medications, and other drugs severely impair gut as well as lung microbiota. Resulting dysbiosis and reduced microbial diversity dysregulate the bidirectional crosstalk across the gut-lung axis, resulting in hypersensitivity and hyperreactivity to respiratory and food allergens. Efforts are undertaken to reconstitute the microbiota and immune balance by probiotics and engineered bacteria, but results from human studies do not yet support their efficacy in asthma prevention or treatment. Overall, dysbiosis of gut and lung seem to be critical causes of the increased emergence of asthma.

Keywords: Allergy; Antibiotics; Asthma; Microbiome; Probiotics; Th2 inflammation.

Fig. 1

A Bacterial taxonomy: classification of the organisms in a rank-based classification (left) and exemplary taxonomical classification of Moraxella ssp according to bacterial taxonomy (right). B Distribution of common phyla and genera in the airways of healthy and asthmatic subjects: The graph depicts the relative abundance (in %) of the five most common phyla of bacteria colonizing the human airways and lung in healthy (white bars) and in asthmatic (black bars) subjects. Phyla Actinobacteria, Firmicutes and Bacteroidetes are less abundant in airways of asthmatics, while Proteobacteria are enriched. The table includes bacterial genera that seem to have a growth advantage in asthmatic airways, such as Moraxella and Haemophilus from Proteobacteria. In contrast, some genera are less abundant in asthmatics such as Prevotella and Corynebacterium, leading to a dysbiosis of the airway microbiome

Fig. 2

Environmental factors associated with asthma and their influence on the gut-lung axis. Environmental factors can have a positive/protective effect (green circles) or a negative/enhancing effect (red circles) on asthma development. For some of these factors (e.g., antibiotics, pollution), it was demonstrated that they are able to interfere with the gut and/or lung microbiome, leading to dysbiosis and disturbances in the bidirectional exchange via the gut-lung axis, thereby enhancing asthma prevalence. Protective factors such as farming environment or intake of probiotics account for lower asthma incidences, but the direct impact on the gut or lung microbiome still needs to be analyzed in more detail