As hallmarks of the coronavirus known as SARS-CoV-2, respiratory infections can lead to inflammation, pneumonia and even death.
Lung epithelial cells act as the first line of defense against pathogens. In addition, these cells can trigger microbial defense, enhancing innate and adaptive immune function in the lower respiratory tract.
Microbes in the respiratory tract
Once thought to be sterile, the respiratory tract actually abounds with microbes including bacteria, viruses, fungi, and archaea. Notably, the lungs harbor a distinctly different microbiome than the gastrointestinal tract does due to stark differences in conditions on their epithelial surfaces; immune system interactions also differ.
The respiratory tract microbiome and lung inflammation: a two-way street presents an excellent overview of the mechanisms and research into these differences. The paper appeared in Mucosal Immunology.
In addition, the authors note the diverse microbiomes in the nasal, oral, upper airways and lower airways of the respiratory system. Disease, aging and smoking can all markedly alter the nasal and oral microbiota.
Respiratory microbiota and immunity
The respiratory microbiome both impacts AND is impacted by immunity and disease. The interaction between the microbiota and the airway epithelium may be one key to preserving immune homeostasis.
Viral infections, such as respiratory syncytial virus influenza, and even rhinovirus (common cold) can alter the long-term immune response of the lung.
In addition, changes in abundance and diversity in the lower respiratory tract microbiome are associated with pulmonary disease such as chronic obstructive pulmonary disease, asthma, cystic fibrosis and lung cancer. A shift often occurs towards Gammaproteobacteria, the bacterial class that contains many common lung-associated pathogens such as Haemophilus and Pasteurella species.
Pathogens in lung inflammation
Gammaproteobacteria thrive on byproducts of inflammation; catecholamines, inflammatory cytokines, increased temperature, and free ATP. Also, nutrient supply for bacteria in the airways (limited during health) is abruptly increased by the presence of mucus and vascular permeability.
Making the situation worse, Gammaproteobacteria also drive further inflammation and can out-compete bacteria that do not benefit from inflammation. A cascade of unregulated inflammation is an underlying cause of many lung diseases.
In contrast, Prevotella species in the oral cavity may enhance immunologic homeostasis of the airways, report the authors.
Researchers are seeking answers: does an altered lung microbiome initiate disease, promote chronic inflammation, or is it a marker of injury and inflammation?
One tangential example: In a 2019 study with mice exposed to cigarette smoke for 2 hours per day for 90 days, inflammatory mediators were linked with specific microbiomes. In addition, members of Proteobacteria phyla and Firmicutes phyla played a key role in keeping homeostasis.
Like tobacco smoking, pathogens can cause local or systemic inflammatory responses.
Lung microbiome manipulation to change disease progression
The nature of the problem—inflammation—suggests that microbes may have a modulating effect.
Microbes are important immunomodulators, spawning regulatory T cells that can turn off inflammation. For example, this anti-inflammatory effect is thought by researchers to be a possible mechanism for the benefit of probiotics in asthma. IPA addressed the topic previously in a blog: As Asthma Rates Rise, So Does Interest in Microbes.
Another recent article by IPA — COVID-19: A Role for Probiotics in Immunity? — dives into the evidence for probiotic benefit in viruses, predominantly influenza.
Probiotics may also stimulate peripheral blood monocytes cells (PBMCs), which leads to improvement in immune biomarkers. In a 2015 study, a combination of strains of Lactobacillus salivarius and Bifidobacterium breve decreased the secretion of proinflammatory cytokines via PBMCs. Note that strain is crucial because impact varies by strain; each probiotic strain is a unique organism, quite different in effect.
Probiotics have been shown to be of some benefit with viral infections of the upper respiratory tract. But when it comes to SARS-CoV-2, few facts are known except that it apparently targets the lungs.
Respiratory health is key. The lung microbiome and cells of the airways interact in complex ways with immune cell regulation.
And when it comes to health, a dose of prebiotics and probiotics daily, whether through food or supplements won’t hurt.