Electronic Thesis/Dissertation
 

Assessing the Gut Microbiome Response to Fecal Microbiome Transplantation in Children with Recurrent Clostridioides difficile Infection

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Exposure to broad-spectrum antibiotics (e.g. vancomycin and metronidazole), which can disrupt the composition of a patient’s gut microbiome, increases susceptibility to Clostridioides difficile infection (CDI). In contrast to antibiotic therapy, fecal microbiome transplantation (FMT), consists of transferring fecal material from a healthy donor to a patient’s gastrointestinal tract to restore a healthy gut microbial diversity. In this study, we established donor-patient pairs (n=9) to assess the gut microbiome bacterial composition of our samples and observe longitudinal compositional changes post-FMT. Samples were sequenced on a single run using the Illumina HiSeq3000 platform, with an average of 8,670,338 paired-end reads. PathoScope 2.0 was used to map cleaned metagenomic reads to the NCBI prokaryotic representative and reference sequence database for taxonomic classification. Furthermore, additional analyses were applied to assess the potential implications of FMT, including the acquisition and elimination of antimicrobial drug resistance (AMR), potential pathogens, and functional microbial pathways. All patients presented with complete resolution of CDI symptoms. With FMT, there was a decrease in the phylum Proteobacteria (p<0.001) and an increase in the phyla Bacteroidetes (p=0.011) and Firmicutes (p=0.067). Moreover, there was a decrease in AMR genes (p<0.001) and potential pathogens (p<0.001), thereby resembling the levels identified in their respective donors. Biosynthetic pathways also predominated in patients post-FMT. Overall, our patients presented with reduced levels of AMR genes and potential pathogens as well as increased species diversity and richness with FMT.

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