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