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Kazemian, Negin

University of British Columbia

The intricate nexus between humans, environmental factors, and the gut microbiota plays a pivotal role in determining the overall health of the host. Our gut microbiota's composition is a dynamic tapestry woven from threads of both early-life events and adult experiences, each contributing uniquely to our overall health and well-being. Thus, the overall aim of this thesis was to investigate the role of the gut microbiome in health and disease states. The gut microbiota’s role in cholesterol metabolism (cholesterol to coprostanol conversion), is not fully understood. Therefore, I first aimed to explore the gut’s environment, encompassing mucus, microbiome, and metabolites to explore its relationship with cholesterol metabolism among healthy participants. High-converters had increased Akkermansia muciniphila. Importantly, the causal role of A. muciniphila in conversion was confirmed. Non-converters showed reduced mucus glycan sialylation and fecal bile acid desulfation, similar to trends observed in inflammatory bowel disease (IBD). Next, I aimed to gain a holistic understanding of the impact of adverse childhood experiences (ACEs) on gut microbiota. ACEs can impact physical and mental health outcomes in adulthood; however, studies assessing how ACEs may impact gut microbiota are lacking. High ACE individuals displayed distinct gut microbiota differences potentially impacting intestinal tissue integrity. They also experienced a higher prevalence of diarrhea, possibly linked to stress on the gastrointestinal system. Lastly, I aimed to better understand the underlying mechanisms for fecal microbiota transplantation (FMT) and optimize microbial therapeutics for recurrent Clostridioides difficile infections (rCDI). Studies often have a uni-kingdom focus and few studies have examined the role of gut mycobiome and virome on FMT efficacy. Thus, I aimed to investigate whether FMT super-donors exist or whether the gut microbiomes of both donors and recipients are implicated in FMT success. Our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients but also on the interactions between the donor and recipient microbiomes. In summary, our integrated studies underscore the multi-faceted factors involved in microbiome-mediated mechanisms in health and disease states. Insights gathered can pave the way for innovative therapeutic interventions against diseases and microbiota-related conditions.

Text

2024-10-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87727

Mechanical Engineering

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/