Date of Award

January 2020

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Melinda M. Pettigrew

Abstract

Clostridioides difficile is an opportunistic enteric pathogen that can cause a range of symptoms in humans from diarrhea to pseudomembranous colitis. The risk of recurrence of C. difficile infection after initial treatment with antibiotics is high. Although prior studies have sought to understand the link between the human gut microbiome and the risk of recurrence, none have utilized shotgun metagenomic sequencing methods to establish a relationship between microbiota diversity and recurrence risk. In this study, stool samples were obtained from 47 patients at Yale New Haven Hospital who tested positive for an incident C. difficile infection. Shotgun metagenomic sequencing was used to characterize the abundance and diversity of the microbiota and the antibiotic resistome of each sample. The association between taxonomic diversity of the gastrointestinal microbiota and the risk for recurrence, case definition, and patient characteristics was analyzed. There was a significant association between age and the risk for recurrent infection, with older patients more likely to experience recurrence. Linear discriminant analysis effect size revealed that certain taxonomic groups were differentially prevalent in patients with and without a recurrent episode and in patients with community-acquired infections vs. those with hospital- or healthcare-associated infections. Those who experienced a recurrent infection had a higher abundance of Blautia producta, and a lower of abundance of Gardnerella vaginalis and Eggerthella lenta than patients who did not experience a recurrence. The microbiota of patients who had a community-acquired infection were more likely to include protective bacterial species and bacteriophage, such as Bacteroides, Faecalibacterium prausnitzii, and crAssphage. This study provides a preliminary exploration into the association between the human microbiome and the risk of C. difficile recurrence and demonstrates the value of using shotgun metagenomic sequencing for further investigation.

Comments

This is an Open Access Thesis.

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