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Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma


Paradigms of Lung Microbiota Functions in Health and Disease, Particularly, in Asthma

Elliot Mathieu et al. Front Physiol.


Improvements in our knowledge of the gut microbiota have broadened our vision of the microbes associated with the intestine. These microbes are essential actors and protectors of digestive and extra-digestive health and, by extension, crucial for human physiology. Similar reconsiderations are currently underway concerning the endogenous microbes of the lungs, with a shift in focus away from their involvement in infections toward a role in physiology. The discovery of the lung microbiota was delayed by the long-held view that the lungs of healthy individuals were sterile and by sampling difficulties. The lung microbiota has a low density, and the maintenance of small numbers of bacteria seems to be a critical determinant of good health. This review aims to highlight how knowledge about the lung microbiota can change our conception of lung physiology and respiratory health. We provide support for this point of view with knowledge acquired about the gut microbiota and intestinal physiology. We describe the main characteristics of the lung microbiota and its functional impact on lung physiology, particularly in healthy individuals, after birth, but also in asthma. We describe some of the physiological features of the respiratory tract potentially favoring the installation of a dysbiotic microbiota. The gut microbiota feeds and matures the intestinal epithelium and is involved in immunity, when the principal role of the lung microbiota seems to be the orientation and balance of aspects of immune and epithelial responsiveness. This implies that the local and remote effects of bacterial communities are likely to be determinant in many respiratory diseases caused by viruses, allergens or genetic deficiency. Finally, we discuss the reciprocal connections between the gut and lungs that render these two compartments inseparable.

Keywords: asthma; gut; gut-lung axis; immunity; lung; microbiota; physiology.


The lungs should be considered as an ecosystem with its own microbiota. (A) Maintenance of balance in the lung microbiota: the communities of micro-organisms in the lungs are shaped by microbial immigration and elimination [adapted from (Dickson et al., 2014)]. (B) From birth onwards, the lungs are continually exposed to diverse micro-organisms. This diversity of bacterial exposure, the environment and any treatments administered may play a fundamental role in determining susceptibility to pulmonary disease. (C) In a healthy individual, the load of micro-organisms in the lungs is equivalent to 103–105 bacteria per gram. Proteobacteria, Firmicutes, and Bacteroidetes are the main phyla present. Asthma is associated with a shift in the lung microbiota toward greater diversity and species richness.
This ecosystem is shaped by lung physiology, which changes radically from the upper respiratory tract to the alveoli. Indeed, in the trachea, the airway has a diameter of about 15 mm, and the partial pressures of oxygen and carbon dioxide are similar to those in the external environment. Temperature and contact area are low. Moving toward the alveoli, temperature, contact area, and the partial pressure of carbon dioxide increase, whereas the partial pressure of oxygen and airway diameter decrease. The barometric pressure in the lung is dependent on pulmonary ventilation. At steady state (no air flow) the pressure is similar in the alveoli and in the external environment. During inspiration and expiration, the pressure falls, and increases, respectively. The airway environment also changes and may favor the selection of certain bacteria, leading to the installation of pathogens.
The high rate of renewal of the intestinal epithelium and the diversity of the populations of cells in the intestinal mucosa, comprising immune, absorptive and secretory cells, create a large, flexible arsenal of innate, and acquired defenses against a dense microbiota. Studies in germ-free (GF) mice have shown that normal gastrointestinal tract development is dependent on the presence of a commensal microbiota. The epithelial cell monolayer is linked and maintained by the apical junctions, consisting of adherens, and tight junctions (Miyoshi and Takai, 2005). The regulation of apical junctions is crucial, to prevent the translocation of bacteria, or molecules through the cell monolayer. The lungs appear to be less affected by the absence of a microbiota than the gut. The levels of B cells, T cells, conventional dendritic cells (cDC), and plasmacytoid dendritic (pDC) cells are similar in GF mice and SPF mice. The only major differences between GF and SPF mice are that PD-L1 expression is stronger in SPF mice, whereas GF mice have higher iNKT levels (both in the lungs and the gut) than SPF mice.
Gut-lung communication. Extensive studies have assessed the local impact of a particular microbiota on organs. Over the last few years, researchers have become interested in the possible crosstalk between different sites within the body. The gut-brain axis is the best known example of this, but the gut-lung axis has also attracted attention. Few data are available for the gut-lung axis, but environmental products and bacteria can be translocated from the gut to the lung (and vice versa) via oropharynx reflux and micro-aspiration. The bloodstream may also serve as a route of communication between the lungs and the gut. Changes to the gut microbiota, such as the modulation of segmented filamentous bacterial load, may influence the outcome of Staphylococcus aureus pneumonia in the lungs.

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