Airway Microbiome for Asthmatics

Understanding the role of the airway microbiome in the development and progression of asthma may lead to new treatments or more effective administration of current therapeutics, says a review article from a team of investigators at Le Bonheur Children’s Hospital published in Frontiers in Pharmacology. The review explored the relationship between the airway microbiome and asthma alongside other intrinsic and extrinsic factors, with particular emphasis on how these factors impact asthma development and severity in pediatric and Black populations as high-risk groups. This review was co-authored by Emergency Medicine Physician Mark A. Snider, DO, Chief of Pediatric Pulmonology, Allergy, Immunology and Sleep Medicine Patricia J. Dubin, MD, and Director of the Asthma Research Program and Plough Foundation Chair of Excellence in Pediatrics Amali E. Samarasinghe, PhD.

“Crosstalk between the mucosal microbiota and the immune system as well as the gut-lung axis have direct correlations to immune bias that may promote chronic diseases like asthma,” said Dubin. “Asthma initiation and pathogenesis are multifaceted and complex with input from genetic and environmental components.”

Composition and Development of the Airway Microbiome

When comparing the airway microbiome, which includes bacteria, viruses and fungi, a microbiome of high density and low diversity is associated with inflammation. Historically, bacteria have been associated with asthma exacerbations, severity of disease and how individuals respond to treatments. Patients with asthma generally have a higher abundance of the phylum Proteobacteria (which include a wide range of potentially pathogenic bacteria), while patients with eosinophilic asthma may have increased abundance of the family Enterobacteriaceae and the genus Streptococcus.

The virome of asthma patients is of reduced abundance and diversity of the viruses that attack bacteria, and patients with severe asthma may have an increased virome density that correlates with poor lung function. When looking at the asthma patient lung mycobiome (fungi living in the airway), research has shown that significant fluctuations, with the loss of good fungi and the proliferation of pathogenic fungi, may promote the development of asthma.

Le Bonheur Emergency Medicine Physician Mark A. Snider, DO, Director of the Asthma Research Program Amali E. Samarasinghe, PhD, and Chief of Pediatric Pulmonology, Allergy, Immunology and Sleep Medicine Patricia J. Dubin, MD, (pictured left to right) recently published an article reviewing how the airway microbiome affects asthma development and severity. The team hopes that understanding more about the intersection of asthma and the microbiome could lead to new and more effective treatments.

“Existing literature on the airway microbiome has compellingly demonstrated differences in microbial diversity and composition between asthma patients and healthy subjects,” said Samarasinghe. “Furthermore, there may be significant differences in the airway microbiome in asthma patients of different ethnicities or racial groups that may impact disease progression and may require personalized therapeutic approaches.”

Research also shows that the time between infancy and early childhood is critical for the development of the immune system and the typical microbiome. Early life airway microbiota play a role in the regulation of the immune system to impede the development of allergic asthma. Lack of microbial colonization in this critical period increases total immunoglobulin E (IgE), airway eosinophils and airway resistance in laboratory models. Another risk factor for asthma development is cesarean section as it may place newborns at a risk of viral infections during infancy and childhood. Researchers say this is a concern as C-sections are increasing globally, with Black women more likely to have a C-section, which correlates with asthma prevalence and severity.

The Role of the Gut-Lung Axis

While the airway microbiome is important to asthma development and severity, researchers also looked at the gut-lung axis and how this might impact asthma patients. It is postulated that the microbiota of the gut and lungs may cross-regulate as the respiratory and gastrointestinal tracts share a common embryonic origin. Certain gut bacteria were more abundant in Black women, showing a link between the gut microbiome and disease susceptibility and severity in terms of race. Researchers noted that the observed variation in microbiome may be a result of socioeconomic differences rather than inherent biological factors.

“Differences in gut microbiota have been associated with disease susceptibility by race and sex,” said Samarasinghe. “Analysis of the gut microbiome may be a simple and early biomarker for disease predisposition.”

Factors Affecting the Microbiome

The review looked at additional factors that affect the airway microbiome and thereby might have an impact on asthma development and severity. Genetics can impact microbiome composition, and smoking can disrupt the relationship of normal microbiota in the upper and lower airway. Black smokers have more negative consequences of smoking, including asthma, compared to White smokers, and third-hand smoke exposure, particularly for children, can cause an alteration in the airway microbiome.

Diet and nutrition can impact the microbiome — particularly gut microbiota — in myriad ways. Obesity associated inflammatory responses can ultimately lead to asthma. Breastfed infants have lower incidence of hypersensitivity to allergens and subsequent asthma development than infants who are not breastfed. Nutritional factors may also explain race-related differences in asthma development. Incorporating fiber-rich foods led to significant alterations to the gut microbiome and improved mucosal health in Black populations. Vitamin D (which can alleviate asthma severity) deficiencies are correlated with asthma in Black children.

“The link between diet and microbiota is evident from the co-occurrence of malnutrition and gut dysbiosis,” said Samarasinghe. “A diet that is rich in nutrients and dietary fibers can result in a diverse gut microbiome that is favorable for host immunity and health. A compromised diet not only affects the intestinal health, but also leads to chronic pulmonary disorders such as asthma.”

Drugs also impact the microbiome of asthma patients and can impede the ability for some medications to function properly. Antibiotic use can increase asthma severity as they alter the gut and lung microbiome richness, evenness and composition. Corticosteroids are also associated with alterations to the airway microbiome including overall reduction in bacterial diversity and richness.

“The risk factors for the pathogenesis and severity of asthma are multifactorial. Whether race contributes to asthma severity and outcomes more as a biological factor or a social construct is unclear, but what is clear is that higher prevalence, higher severity and worse outcomes are associated with the Black race as defined in literature,” said Snider.

This review shows the important role that the microbiome plays in asthma and discusses the various factors that influence the diversity and richness of the microbiome. Further research is needed to understand how the airway microbiome participates in asthma pathogenesis in order to develop new and more focused treatments and therapeutics.

Postdoctoral Scholars Armando Flores-Torres, PhD, and Sandesh Marathe, PhD, at the University of Tennessee Health Science Center are also co-authors of this review article.