"Acute gastroenteritis has a major disease burden worldwide. There are 2.3 billion cases of acute gastroenteritis worldwide each year that accounts for 8% of all deaths in children under the age of 5. In the United States, there are an estimated 179 to 375 million cases annually. Gastroenteritis can have acute and chronic effects on human health. Pathogens often are not identified in cases of acute gastroenteritis due in part to the wide range of causative agents and the difficulties with standard culturing practices. The advent of next-generation sequencing has allowed the study of the intestinal microbiome to detect alterations in the composition as specific disease signatures. There have been few studies on the microbiome of gastroenteritis, but none have to date have studied both the virome and bacteriome together. Through this combined analysis, a deeper understanding of gastroenteritis can be generated.In this dissertation, the Microbiome (Virome and Bacteriome) of 79 cases and 125 member controls were examined. It was found that cases had lower diversity and richness in and increased abundances in Enterobacteriaceae. Additionally, associations with severe illness were made to a specific cluster of samples. Differential abundance analysis identified the involvement of both viruses and bacteria. Analysis of the same 79 cases in a recovery state (n = 63), identified the changes that occur during and after infection. These changes agree with the case and control analysis. The functional aspects were analyzed of the viral communities. Three novel bacteriophages were isolated from stool samples and characterized. Two of the bacteriophages were determined to be lysogenic and were found in 23 additional E. coli O157:H7 strains based on BLAST alignments. One of the lysogenic bacteriophages (PHG003), harbors an SbcC gene which is a predicted exonuclease but it's important to the host bacterium remains unknown. Additionally, a lytic bacteriophage (PHG001) was also isolated and exhibited a relatively broad host range and was incredibly virulent to E. coli O157:H7. Additionally, PHG001 exhibits a phage-antibiotic synergism with the use of ampicillin and mitomycin c. Either antibiotic with the bacteriophage exhibited a drastic reduction in bacteria growth. PHG001 also reduced shiga toxin expression compared to control levels."--Pages ii-iii.
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