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Glycan-Mediated Context Dependency: Influence of Carbohydrate Composition and Mucin-Coated Surfaces on Community Structure and Metacommunity Stability
The gastrointestinal microbiome is growing in interest as a target for nutritional and medical intervention for personalized, holistic approaches to medicine that prevent or treat a variety of diseases. With the development of various interventions for the gastrointestinal tract, difficulties arise in predicting outcomes due to the complexity of the microbiome. Many approaches to screening intervention methods are still naïve from an ecological perspective, primarily focusing on attempts to predict outcomes by genomic potential of organisms to respond to a treatment or by screening outcomes in models. While these methods can identify powerful interventions for health, the responder vs non-responder phenomenon is of great concern and interest among microbiome researchers. This is particularly relevant because some responder/non-responder outcomes are hypothesized to be because of ecological effects, such as competitive exclusion of administered probiotics by an autochthonous strain, or indirect effects on populations through microbial interactions. While some groups have been working on characterizing the governing rules in microbiomes and microbial communities, there is still much greater focus on average outcomes of interventions and mechanisms of individual microbes. I hypothesized that our understanding of rules governing microbial metacommunity dynamics under various chemical contexts could be improved by leveraging in vitro models, population-based models, and ecological theory. In this thesis, I describe my work to (1) improve understanding how different contexts can modulate microbial community composition and the structure of interspecies interactions due to variation in carbohydrate composition of the medium, (2) characterize the role of a mucin-associated sessile communities on the resistance and resilience of a metacommunity to vancomycin perturbation and (3) develop a computational tool for simulating these metacommunity dynamics with consideration for deterministic niche-based effects and dispersal. Through this work, I have developed methods and tools that may allow us to improve approaches for screening cultured microbial communities for context-dependent interactions and propose considerations for a metacommunity perspective of the gastrointestinal microbiome.
McCullough, Hugh C, "Glycan-Mediated Context Dependency: Influence of Carbohydrate Composition and Mucin-Coated Surfaces on Community Structure and Metacommunity Stability" (2023). ETD collection for University of Nebraska - Lincoln. AAI30575750.