Specific Aims

Specific Aims:
In recent decades, asthma has become epidemic. In the U.S., 1 in 12 individuals have a diagnosis of asthma, and direct and indirect costs total $56 billion annually, compared to 1 in 24 and $6 billion in 1990. Asthma is characterized by both pulmonary and systemic inflammation that influence both the severity of the disease and the quality of life in those with asthma. The degree of inflammation in asthma is associated with decline in lung function, increased frequency of exacerbations, anxiety and depression, and decreased functional and health status. In order improve quality of life, and lower health care costs, a better understanding of contributing factors to the inflammation which drives this pervasive disease is critical. Epidemiological evidence suggests that a diets high in fiber are associated with a reduced risk of asthma as well as contributing to decreased inflammation, although the mechanism(s) for this effect remains unknown. Our recent pilot research has shown that dietary fiber intake is associated with improved lung function and that fiber intake modulates short-chain fatty acids (SCFAs) produced by the gut microbiome. Our overarching hypothesis is that low-fiber diets alter the gut microbiome in asthma patients and leads to decreased SCFAs derived from gut bacterial fermentation of fiber, resulting in increased systemic and pulmonary inflammation, one of the hallmarks of asthma. Further elucidating these relationships is of utmost importance given downstream implications for possible therapeutic strategies. We will investigate these relationships in a collaborative effort with Johns Hopkins University (JHU), which will include extensive clinical and bio-behavioral phenotyping of a population of adults with chronic asthma. This proposal is structured around the following specific aims:

Specific Aim 1: Determine the feasibility of a high fiber (high in fruit and vegetables and fiber-rich whole grains) and a low fiber diet feeding study among obese adult females with asthma and assess self-management strategies. We hypothesize that the intervention will prove feasible, based on acceptability of meals and meal delivery, recruitment and retention, and dietary adherence [This Aim is funded through a KL-2 award at JHU]

Specific Aim 2: Demonstrate the impact of low and high fiber diets on the gut microbiome composition and its effect on bacterial metabolites and inflammatory mediators among those with asthma. We hypothesize that increased fiber intake will be associated with a shift in the gut microbiome structure towards an increase in bacteria of the phylum Firmicutes, and a consequent increase in systemic and airway concentrations of SCFAs, most notably butyrate. We also hypothesize
that high fiber diets and elevated systemic and airway SCFAs are associated with decreased concentrations of inflammatory biomarkers.

Specific Aim 3: Determine the influence of high and low fiber diets on the functionality of the gut microbiome in terms of ability to ferment dietary fiber and produce beneficial short-chain fatty acids. We hypothesize that in vitro fermentation of SCFAs from fecal donors is modified by dietary fiber intake. Moreover, we hypothesize that systemic and airway inflammation in asthma patients is influenced by gut SCFAs arising from the microbial fermentation of dietary fiber. Our analysis of high and low fiber diets in relation to the gut microbiome, short chain fatty acid production and inflammation will contribute a missing, fundamental element to our knowledge base and thereby expand our understanding of how variations in diet affect asthma. Our study is innovative in that this is the first study to date that will provide an integrated approach to the effect of dietary fiber, the gut microbiome, SCFAs and the lung. There is an urgent need to develop management strategies for asthma, given that current therapies to attenuate the inflammation of asthma and resulting consequences are limited. This study will provide direct support and inform future interventional studies targeted at the management and prevention of asthma through self-management of diet. Data gathered from this project will provide necessary data for a planned R01 resubmission, and proof of concept for a lung-gut axis.