In United States alone, more than 1 in 4 children are diagnosed with some form of allergy, yet the exact etiology of allergy development in childhood is unknown. Many factors have been associated with this rise in such disorders including genetics, epigenetics, environmental toxins and particulates, as well as the microbiota. The host microbiome has been associated with a multitude of human and animal diseases, disorders, and conditions. Its involvement in the atopic and autoimmune disorders is an every-growing field of new knowledge. In this work, I explore the effect of the gut microbiome on allergy, specifically childhood eczema and asthma, using samples and data collected from the Isle of Wight allergy study cohort as well as a fecal-transplanted humanized microbiota mouse models. In addition, measured specific gut metabolites that were significant in distinguishing between the pathology phenotypes in both study sets will be discussed. In chapter 1, I explored the gut bacterial microbiota of infants in the Isle of Wight allergy study cohort and their association with their development in eczema. We also explored bacterial taxa previously shown in published work to be associated with allergy as agonists or antagonists. Subsequent statistical analyses including random forest and logistic regressions supported these findings and results from logistic regressions provide statistical significance for the association of eczema status at age 3 months with the relative abundance of genus Veillonella at that age. In chapter 2, a study conducted using a mouse model of asthma created by fecal transplantation of the infants featured in chapter 1, connection between gut microbiota in infancy and lung baseline responses were studied and supported. In chapter 4, the role of the gut metabolome in the development of allergic phenotype was explored using the samples from both chapters 1 and 2, where it was shown that infants with allergic phenotype have a distinct gut metabolomic profile compared to infants without allergic phenotype; and mice with reduced lung functionality expressed a distinct gut metabolic profiles compared to mice without reduced lung functionality. Overall, these studies confirmed previously associated relationship between specific bacterial taxa and allergy using a unique infant cohort as well as an original mouse model, while also providing new points of interest to further deepen the understanding of the relationship and the interaction between the gut contents and the host’s development of allergy.
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