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Understanding and Controlling the Effects of Dietary and Viral Factors on Intestinal Health and Allergy

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Abstract
The rate at which the human diet has changed in recent centuries has surpassed that of our evolution. As a consequence, this could be deleterious to health. The gut microbiome is the collection of all microbiota and their genetic contents found within the gastrointestinal tract, and has been found to influence health in numerous ways. Its profound impact on the human body is essential for health and is heavily influenced by diet. As diet is a modifiable target, modulation of the gut microbiome through dietary intervention, such as through pre-probiotics, is of interest. Three different dietary ingredients (walnuts, frankincense, and Bifidobacteria) were evaluated for their preprobiotic effects on gut microbiota composition, function and allergic disease. Models to study the effect of norovirus, a pathogen known to cause gastroenteritis, on food allergy and gut microbiota were also established. Walnuts have been shown to positively affect gut health, cognitive function and cancer, yet their effect on host metabolism is not well defined. The work presented here suggests that walnuts to change the gut microbiota composition to induce more short chain fatty acid-producing bacteria. Along with this, metabolic changes in mice fed walnuts were observed, including a decrease in respiratory exchange ratio and increased activity. These changes could be due to the prebiotic effects of walnut composition, including fiber or polyphenol content. These findings suggest that walnuts may have prebiotic effects on the gut which leads to positive changes in metabolism. Boswellia serrata, commonly known as frankincense, has been used for medicinal purposes for centuries, including treatment of asthma. However, the effect of consumption of a primary bioactive ingredient of it, 3-O-acetyl-11-keto-b-boswellic acid (AKBA), on the gut microbiome is not known. In our work, we investigate the effect AKBA consumption has on the gut microbiota and health of both healthy and allergic asthma-induced mice. In healthy mice, AKBA significantly decreased gut bacterial richness in male mice but had no effect on female mice. Akkermansia muciniphila, previously reported to be associated with weight loss and anti-inflammation, was found to be significantly increased in both male and female mice, along with an increase in Bifidobacterium in female mice. These results show the potential benefits of dietary Boswellia serrata due to the modulation of gut microbiome composition, along with potential sex-based differences in its effects. Given its ability to shift the microbiota composition, as well as the fact our intestinal bacteria can significantly affect the development of allergies, the impact of Boswellia serrata acid on allergic asthma was explored. Allergic asthma is the manifestation of an allergy in the lungs, which leads to coughing, wheezing and difficulty breathing. The gut microbiome composition has been shown to effect asthma development and exacerbation. In our study, we tested AKBA’s effect on development and severity of asthma and gut bacteria. AKBA treated mice showed significantly lower weight and airway inflammation. Asthma control mice showed a decrease in overall bacterial diversity while AKBA treated mice had increases in several bacterial genera associated with anti-inflammatory effects, including Bifidobacteria. The Bifidobacteria was further isolated from stool and identified via ITS sequencing as B. pseudolongum in all isolates. Further testing of B. pseudolongum via oral administration showed an alleviation in airway inflammation, suggesting Boswellia serrata has potential to serve as an anti-asthma agent via alteration of the microbiome and increases in B. pseudolongum. Although the aforementioned dietary interventions appear to affect the gut microbiota and allergy, the effects of enteric viral infection on allergies have not directly been investigated. For this dissertation, two animal models, one targeting food allergy and the other norovirus, were developed to help study this proposed correlation. Further work should be continued on the extent norovirus has on allergic diseases and the microbiome.
Type
dissertation
Date
2023
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