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Evaluation of Soluble Fiber as a Strategy to Decrease Asthma Morbidity in Pediatric Populations

$462,653U54FY2025MDNIH

Northern Arizona University, Flagstaff AZ

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Abstract

PROJECT SUMMARY Approximately 7.7% of the US population have asthma, and incidence has been increasing since the 1980s. In Arizona, asthma prevalence exceeds the national average, with the majority of asthma diagnoses made in the Phoenix Metropolitan Area. Genetic risk factors have been identified in asthmatics. However, the steady increase in the prevalence of asthma in the US population suggests that environmental exposures or other extrapulmonary factors, such as diet and the gut microbiota, may play a critical role in asthma development. Differences in asthma prevalence and morbidity are highlighted in individuals from urban areas where dietary intake of nutrients such as fiber, are historically low. For example, poor-urban residence is an individual risk factor for reporting an asthma attack and having higher odds for an asthma-related visit to the Emergency Department. These populations are more likely to experience differences in nutritional intake, notably a diet low in fiber. A low fiber diet leads to shifts in the gut microbiome and may explain differences in asthma risk. Dietary fibers are complex carbohydrates that resist metabolism in the small intestine by host enzymes and are fermented in the colon by resident microbes. Gut microbial fermentation of soluble fibers results in production of metabolic by-products such as the short chain fatty acids (SCFAs) acetate, propionate, and butyrate, which are important molecules that act as a link between the microbiota and host immune system. We hypothesize that a low fiber diet is a critical, but understudied, factor in asthma morbidity. The overall goals of this proposal are to determine the effect of a gut microbiome modifier (fiber) on microbial composition and function in a resource-limited population. In addition, we will determine the effect of soluble fiber supplementation in reducing airway inflammation via the gut microbiome-airway axis. The hypothesis governing this proposal is that gut microbial metabolism of dietary fiber to SCFAs will reduce airway inflammation by altering the phenotype of T cells and eosinophils. We have assembled a strong team of clinicians and scientists, and we draw on our pilot study of fiber intervention in a pediatric asthma cohort to achieve 3 aims. First, we will build on the community partnerships through the PCH Mobile Asthma Clinic (Breathmobile) to assess baseline fiber consumption and gut microbiota across different locations in Maricopa County. Second, we will evaluate the effect of a soluble fiber supplement in a pediatric asthma cohort. Finally, we will evaluate the effect of microbial-derived SCFAs on key immune cell populations. Completion of these aims will provide evidence that can guide public health nutritional interventions to improve outcomes in pediatric asthma.

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