Investigating the host-associated microbiome in biomedicine : insights from experimental models, host genotype effects, and disease implications

Human microbiome research has expanded exponentially, revealing the presence of microbes in diverse locations in the human body. The microbiome, comprised of a consistent group of phyla, interacts intricately with its host. This co-dependent relationship extends beyond the gut, influencing various aspects of human health and disease. Factors such as host genotype, diet, geography, and lifestyle significantly shape the microbiome, allowing for local adaptation and exerting selective pressures on microbial communities.

In this comprehensive thesis, we delve into critical aspects of microbiome research. The first chapter focuses on refining the Fut2^-/- mouse model, recognizing the necessity for standardized gut microbiomes in experimental reliability. Our findings challenge the efficacy of cohousing as a method for homogenizing microbiota in Fut2^-/- mice, one of the popular standardization method being used in microbiome research. The second chapter explores host FUT2 genotype-dependent dynamics of Bacteroides species, revealing host genotype -associated diversity and nuances between culture-dependent and -independent methods. The study underscores the importance of employing both techniques for a holistic understanding of host-microbe interactions.

The third chapter introduces an innovative, time-efficient method for culture-dependent analysis, addressing the limitations of traditional approaches. This advancement has broad implications for microbiome research, particularly in diseases where microbial composition plays a pivotal role, such as pancreatic ductile adenocarcinoma (PDAC). In the fourth chapter, I discuss the microbiome's involvement in PDAC, emphasizing its potential role in shaping cell clonality.

Overall, this thesis navigates the complex landscape of microbiome research and attempts to unravel the intricacies of host-microbe dynamics.