The lung microbiome is known to undergo changes in various pulmonary conditions, such as asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and lung transplantation. The increased use of antibiotics, especially in children, has been associated with a higher incidence of asthma, which greatly affects the microbiome. Organisms belonging to the Proteobacteria (Haemophilus, Moraxella) and Firmicutes (Streptococcus) phyla have been found to correlate with asthma. An experimental study in mice revealed that replacing Proteobacteria with Bacteriodetes improved asthma symptoms. This coincided with an increase in regulatory T cells and a suppression of the Th2 proinflammatory cytokines involved in asthma's development.

Probiotics have shown promise in maintaining a "normal" microbiome and treating gut infections. Probiotic therapy has also shown potential in patients with chronic lung infections, such as those with cystic fibrosis and upper respiratory tract infections. However, the precise mechanism by which bacteria "protect" the lungs is still not fully understood and likely varies depending on the microorganism.

Bifidobacterium has been shown to activate dendritic cells (DCs) and Toll-like receptors (TLRs), leading to the secretion of IL-10 and retinoic acid. These mediators can induce regulatory T cells, which help downregulate the Th2 inflammatory response associated with asthma. Histamine, a major component of mast cell granules and secreted by Lactobacillus organisms, has been found to prime DCs and stimulate Th2 inflammatory responses in asthma. Additionally, it has been observed that innate lymphoid cells (ILCs) can influence the microbiome by binding to receptors on epithelial cells, thereby altering the interaction between the epithelium and microorganisms. This alteration can potentially promote the colonization of either pathogenic or nonpathogenic microorganisms. However, there is still much to learn from future studies on the lung microbiome.

The most common pathological conditions affecting mucosal tissue are allergic responses, including allergic asthma, allergic rhinitis, and allergies to food and skin. Common allergens for humans include components of inhaled house dust mites, cockroaches, cat dander, bee stings, and peanut ingestion. Penicillin, a widely used drug, is one of the most common allergens. It can bind to numerous endogenous proteins and modify their antigenicity.

As mentioned earlier, the predominant antibody response in mucosa-associated lymphoid tissue (MALT) is IgA. However, in allergic responses, IgE becomes the predominant antibody. This switch is induced by IL-4 synthesized by Th2-primed CD4 T cells. IL-4 prompts antibody-producing B cells to shift from producing IgG antibodies to IgE. IgE binds to mast cells in the submucosa via its crystallizable fragment (constant) region. When the inhaled antigen is reintroduced and migrates from the airway lumen to the submucosa, it binds to the antigen-binding fragment region of the IgE molecule, forming an immune complex (IgE-Ag) on the mast cell's surface.

Finally, the IgE-Ag complexes must crosslink with other IgE-Ag complexes on the mast cell's surface to trigger intracellular signaling pathways. This leads to degranulation and the immediate release of preformed Th2 mediators, such as histamine, heparin, prostaglandins, leukotrienes, IL-4, IL-5, IL-13, and proteases. These mediators are responsible for the characteristic symptoms of asthma, including smooth muscle constriction.
Alterations in the lung microbiome have been shown to be associated with several pulmonary conditions (including asthma, cystic fibrosis, and chronic obstructive pulmonary disease) and with lung transplantation. The increased rate of asthma in children has been linked to the increased rate of antibiotic use, which has a vast effect on the microbiome. Organisms in the Proteobacteria (Haemophilus, Moraxella) and Firmicutes (Streptococcus) phyla have been shown to correlate with asthma. An experimental study in mice showed an improvement in asthma when Proteobacteria organisms were replaced with Bacteriodetes organisms, which coincided with an increase in regulatory T cells and suppression of the Th2 proinflammatory cytokines prominent in the pathogenesis of asthma.
From a therapeutic standpoint, the use of probiotics to maintain a “normal” microbiome has proved useful in treating infectious diseases in the gut, and the use of probiotic therapy in patients with chronic lung infections (e.g., cystic fibrosis, upper respiratory tract infections) have been promising. The precise mechanism or mechanisms by which the bacteria may “protect” the lungs is still poorly understood but probably varies considerably according to the microorganism.
It has been shown that Bifidobacterium can activate DCs and TLRs to secrete IL-10 and retinoic acid, mediators capable of inducing regulatory T cells, which downregulate the Th2 inflammatory response. From a causative perspective, histamine, a major component of mast cell granules and secreted from Lactobacillus organisms, has been shown to have an association with priming DCs to stimulate Th2 inflammatory responses, as seen in individuals with asthma. In addition, it has been shown that ILCs can play a role in influencing the microbiome through their ability to bind to receptors on epithelial cells, thus altering the interaction of the epithelium with the microorganisms and possibly promoting colonization of either pathogenic or nonpathogenic microorganisms. Much is still to be learned and absorbed from future studies of the lung microbiome.
By far the most common pathological conditions associated with mucosal tissue are allergic responses (e.g., allergic asthma, allergic rhinitis, and food and skin allergies). Some common human allergens include components of inhaled house dust mites, cockroaches, and cat dander, as well as bee stings and ingestion of peanuts. One of the most common drug allergens is penicillin, which can bind to many endogenous proteins and also alter their antigenicity.
As previously described, the predominant antibody response in MALT is IgA; however, in an allergic response, IgE is the predominant antibody. It is generated by a switchover mechanism induced by the synthesis of IL-4 from Th2-primed CD4 T cells. The IL-4 induces the antibody-producing B cells to switch over from synthesizing IgG antibodies to IgE. IgE binds to the surface of mast cells in the submucosa through its crystallizable fragment (constant) region of the antibody molecule. Upon reexposure to the inhaled antigen and its subsequent migration from the airway lumen to the submucosa, the allergen then binds to the antigen-binding fragment region of the IgE molecule, which forms an immune complex (IgE-Ag) on the surface of the mast cell.
The final step is that IgE-Ag complexes must crosslink with other IgE-Ag complexes on the surface of the mast cell, which induce intracellular signaling pathways to initiate degranulation and immediate release of preformed Th2 mediators (histamine, heparin, prostaglandins, leukotrienes, IL-4, IL-5, IL-13, proteases). These mediators induce the classical signs of asthma: smooth muscle constriction