The current study aims to explore the role of prebiotic supplementation in adults with and without Asthma/Exercise-Induced Bronchoconstriction (A/EIB). All participants will be asked to consume a prebiotic supplement, and a placebo, each for a total duration of four weeks, separated by a two-week wash out period. The investigators hypothesise that improvements in pulmonary function observed in adults with Asthma following prebiotic supplementation. We hypothesise that improvements in pulmonary function will be attributed, at least in part, to gut microbiota mediated improvements in human immune function.
The current study will investigate the effects of prebiotic supplementation on airway inflammation/bronchoconstriction in adults diagnosed with Asthma/Exercise-Induced Bronchoconstriction (A/EIB). Previous research conducted in adults diagnosed with A/EIB has reported significant improvements in pulmonary function following three weeks of prebiotic supplementation. The significant improvements in pulmonary function were attributed to an attenuation of various markers of airway inflammation, potentially regulated by gut microbiota mediated improvements in systemic immune function. Prebiotics are a type of non-digestible carbohydrate/dietary fibre that can only be digested by certain beneficial bacteria. During the fermentation of prebiotics, beneficial bacteria produce energy/metabolites that can be used to support a variety of human immune functions, such as reducing the level of airway inflammation that occurs following exposure to relevant triggers (e.g. exercise). Imbalances and/or deficiencies in gut bacterial composition/metabolic activity have been identified in children/adults diagnosed asthma. However, the potential mechanisms behind prebiotic mediated improvements in the severity of asthma have yet to be investigated. Participants with and without A/EIB will be allocated two separate nutritional supplements following a double-blind, placebo-controlled design. During the first phase of the nutritional intervention, participants will consume the first supplement (either prebiotic or placebo), for a total duration of four weeks. A two-week wash out period will then be completed before the remaining nutritional supplement is administered for an equal duration. Analyses of key human/bacterial metabolite concentrations will be carried out alongside assessments of immune and pulmonary function, and intestinal permeability at baseline, and throughout all phases of the nutritional intervention. Current understandings of the role of the gut microbiota in the pathogenesis of A/EIB will be expanded through the investigation of novel pathophysiological mechanisms, helping to inform future therapeutic prospects for asthma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
17
Experimental Supplement: HOST-DM059. Participants will be asked to orally consume one powdered sachet each day, at the same time in the morning, reconstituted in tea/coffee/fruit juice, or sprinkled over cereal etc. Whichever method of consumption is chosen, this must be kept consistent across both supplementation phases.
Placebo Comparator: Maltodextrin.
Nottingham Trent University
Nottingham, Nottinghamshire, United Kingdom
Changes In Regulatory T Cell FOXP3 Expression From Baseline To Post Prebiotic Supplementation.
Flow Cytometric Analysis: CD4+ CD25+ IL-10+ Regulatory T Cell FOXP3 Expression (
Time frame: Week 0, Week 4, Week 6, Week 10 (Collected At Rest).
Change In Systemic Immune Function/Inflammatory Markers
Flow Cytometric Analysis: Interleukin (IL)-10, Hematopoietic Prostaglandin D Synthase Enzyme (Pathogenic Effector/Non-Pathogenic Effector TH2 Cells), CD3 (T Cells), CD25 (Regulatory T Cells), Transforming Growth Factor-Beta (TH2 Cells), Fork-Head Box Protein-3 (Regulatory T Cells), CD161 (PETH2 Cells), Interferon-Gamma (TH1 Cells), Live/Dead, Total \& Specific White Blood Cell Counts (Eosinophils, Basophils, Neutrophils, Monocytes, Lymphocytes).
Time frame: Week 0, Week 4, Week 6, Week 10 (Blood Sample Collected At Rest).
Change In Pulmonary Function (FEV1)
% Drop In Pulmonary Function (FEV1) Post EVH = 100\*(Highest Baseline FEV1-Lowest Post EVH FEV1)/Highest Baseline FEV1. Used To Objectively Diagnose Asthma/EIB (\> 10% Drop In FEV1 Post EVH At Two Consecutive Time Points), And Classify Severity As Mild (\> 10% - \< 25% Drop In FEV1), Moderate (\> 25% - \< 50% Drop In FEV1), Or Severe (\> 30%, Or 50% Drop In FEV1 For Patients Receiving/Not Receiving Steroid Based Treatments). All Pulmonary Function Parameters: FEV1, FVC, PEF, FEF25%-75%. \> 10% Reduction = Positive Objective Diagnosis (Asthma/EIB).
Time frame: Week 0, Week 4, Week 6, Week 10 (At Rest & In Duplicate At 3, 6, 10, 15, 20, & 30 Minutes Post EVH).
Change In The Asthma Control Questionnaire - Perceived Symptom Management
Common Asthma Symptoms Management: Night Time Awakening, Upon Waking Symptom Severity, Physical Activity Limitation, Dyspnoea (Breathlessness), Wheezing, Reliever Medication Usage (Rating 0-6).
Time frame: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. (Upon Experimental Trial Arrival During Weeks 0, 4, 6, & 10).
Change In Urinary Metabolite Concentrations
E.G.: Acetic Acid, Propionic Acid, I-Butyric Acid, N-Butyric Acid, I-Valeric Acid, N-Valeric Acid, N-Caproic Acid.
Time frame: Week 0, Week 4, Week 6, Week 10 (Urine Sample) (Collected At Rest & 60 Minutes Post EVH).
Change In The Medication Adherence Report Scale For Asthma (MARS-A)
Asthma Medication \& Nutritional Interventions Adherence Measurement (12 Questions) (Rating 1-5).
Time frame: Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. (Upon Experimental Trial Arrival During Weeks 0, 4, 6, & 10).
Change In 24 Hour Weighed Nutritional Intake Record
Quantitative Measurement - Habitual Nutritional Consumption (Assess Nutritional Intake Consistency Across Experimental Trials).
Time frame: Week 0, Week 4, Week 8, Week 12 (24 Hours Before Experimental Trial).
Changes In Intestinal Permeability Markers
Blood (Serum/Plasma) Based Measurement.
Time frame: Week 0, Week 4, Week 6, Week 10 (Blood Sample Collected At Rest).
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