Improving our understanding of microbiome pathogen colonization resistance through the development of a colon epithelium model
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Citation
Abstract
Recent global burden of disease studies have shown that bacterial infections are responsible for over 13 million deaths worldwide annually, or one in every eight deaths. Increased microorganism exposures and novel strains, reduced focus in research sciences, and dwindling power of current pharmaceutical interventions emphasizes the persistent threat of infectious diseases and demands novel research to address their significant danger to human health. While the risk of infections is ubiquitous, communities in low- and middle- income countries and socio-economically disadvantaged groups in high-income countries face the greatest burden from infections and fatalities, and the prevalence of disease is increasing. One possible factor for disease vulnerability in individuals from disadvantaged communities is gut microbiome dysbiosis and a subsequently compromised ability to resist pathogen colonization. Human microbiomes represent the first line of defense against pathogenic infections and a central place for integrating the effects by the host and their biology, their environment, and pathogenic microorganisms on disease outcomes. This thesis investigates colonization resistance of diarrheal diseases through the creation and utilization of both in silico and in vitro modeling systems to enable the specific exploration of mechanisms relevant to vulnerable communities. A bottom-up agent-based model was created to replicate a simplified colonic microbiome in silico and coupled with in vitro studies of bacterial attributes using a biomimetic mucus hydrogel. The computational model was constructed and stabilized through feedback mechanisms between host epithelium and commensal bacteria, and the chosen environmental perturbances were based on global health research and investigated through in vitro experiments. The model focused on specific mechanisms of colonization resistance between commensal microbiota and pathogen species, and how they could be impacted by relative differences between the species and the conditions of the host. This work has resulted in the development of a useful tool for exploring microbiome mechanisms and presents a methodological framework for investigating colonization resistance of pathogens that has the potential to address the burgeoning threat of infectious diseases worldwide.
Description
2026
License
Attribution 4.0 International