Oral Probiotic Administration to Modulate the Airway Microbiome in Obese Asthmatic Subjects

Oral Probiotic Administration to Modulate the Airway Microbiome in Obese Asthmatic Subjects

Obesity is a major health concern in the Deep South resulting in a growing number of metabolic disorders that strain the resources of our healthcare system. Obesity is recognized as a major risk factor for asthma. The Centers for Disease Control and Prevention (CDC) has stated "obesity is associated significantly with the development of asthma, worsening asthma symptoms, and poor asthma control. This leads to increased medication use and hospitalizations."

Variations in the airway microbiome are correlated with the risk for development of asthma, and populations of different bacteria vary by phenotype amongst severe asthmatics . Proteobacteria are found in greater proportion in asthmatic subjects relative to healthy controls (37% vs 15%) while non-asthmatic subjects have a relative abundance of Firmicutes (47% vs 63%) and Actinobacteria (10% vs 14%) compared to those with asthma . Amongst those with asthma, obese asthmatic subjects have a relative abundance of Bacteroides (54%) and Firmicutes (26%). Notably, both phyla are part of the gastrointestinal microbiome, suggesting inoculation through gastroesophageal reflux which may be more common in obese individuals. Asthmatics identified as having improvement in their asthma control following treatment with inhaled corticosteroids appear to have a greater relative abundance of Actinobacteria (79.8%) in their airways relative to other asthmatics. Actinobacteria have been associated with the production of anti-inflammatory proteins and are speculated to be involved in increasing steroid responsiveness. Other studies have demonstrated that oral administration of probiotics, including Bifidobacterium species within the phyla Actinobacteria, lead to reduced Th2 cytokine production and eosinophilic inflammation, along with promotion of Regulatory T-cell (Treg) populations within the airway. We hypothesize that administration of over the counter oral probiotics containing Actinobacteria (Bifidobacterium) to obese asthmatic subjects will result in decreased airway inflammation and better asthma control by immune modulation.

Inclusion Criteria:

1. Moderate to severe asthma requiring medium to high dose inhaled corticosteroids

   1. Patients will be recruited through the UAB Asthma Clinic and using the UAB Asthma Clinic Database for the Biospecimen Repository
   2. Patients must show spirometry with positive bronchodilator reversibility or have a positive Methacholine Challenge Test within 3 years of enrollment

2. Obesity as defined as BMI over 30

3. Self-reported or radiographic evidence of gastroesophageal reflux disease

4. Ability and willingness to provide informed consent

Exclusion Criteria:

1. Inability of the subject to provide informed consent
2. Inability of the subject to undergo bronchoscopy
3. Use of monoclonal antibody within three months prior to enrollment
4. Use of immunosuppressive medication
5. Use of oral corticosteroids or antibiotics 4 weeks prior to enrollment
6. Use of anticoagulants (warfarin/Coumadin and heparin products).
7. Use of aspirin and/or other non-steroidal anti-inflammatory drugs or clopidogrel (Plavix) within 5 days of bronchoscopy.
8. Pregnancy
9. Diagnosis of HIV, active cancer, or liver disease