Dissertation Defence: Investigating the Human Microbiome: Dynamic Interactions and Therapeutic Potentials in Health and Disease States

Negin Kazemian, supervised by Dr. Sepideh Pakpour, will defend their dissertation titled “Investigating the Human Microbiome: Dynamic Interactions and Therapeutic Potentials in Health and Disease States” in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Mechanical Engineering.

An abstract for Negin Kazemian’s dissertation is included below.

Examinations are open to all members of the campus community as well as the general public. This examination will be offered in hybrid format.

Please email sepideh.pakpour@ubc.ca to receive the Zoom link for this defence.

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ABSTRACT

The intricate interplay among humans, the environment, and the gut microbiota significantly influences the host’s overall health. My gut microbiome is a dynamic tapestry woven from both early-life events and my adult experiences, each contributing uniquely to my well-being. Therefore, this thesis aimed to investigate the gut microbiome’s role in health and disease. Specifically, I sought to understand its involvement in cholesterol metabolism, focusing on the conversion of cholesterol to coprostanol. In my study of healthy participants, I found that high-converters had increased levels of Akkermansia muciniphila, and I confirmed its causal role in conversion. Non-converters exhibited reduced mucus glycan sialylation and fecal bile acid desulfation, reminiscent of trends observed in inflammatory bowel disease (IBD). Moving forward, I delved into the impact of adverse childhood experiences (ACEs) on the gut microbiota. ACEs can influence physical and mental health outcomes in adulthood, but their effects on the gut microbiota have been underexplored. High ACE individuals displayed distinct differences in their gut microbiota, potentially affecting intestinal tissue integrity. They also experienced a higher prevalence of diarrhea, possibly related to stress on the gastrointestinal system. Lastly, I aimed to uncover the underlying mechanisms of fecal microbiota transplantation (FMT) and optimize microbial therapeutics for recurrent Clostridioides difficile infections (rCDI). Many studies have focused solely on bacteria, neglecting the gut mycobiome and virome’s role in FMT efficacy. My investigation revealed that FMT outcomes depend not only on the recipients’ ecological structure but also on the interactions between the donor and recipient microbiomes. In summary, my integrated studies highlight the multifaceted factors involved in microbiome-mediated mechanisms in both health and disease. The insights gained from my research can pave the way for innovative therapeutic interventions targeting diseases and microbiota-related conditions.