Development of Analytical Tools and Animal Models for Studies of Small-Intestine Dysbiosis

Citation

Bogatyrev, Said R. (2020) Development of Analytical Tools and Animal Models for Studies of Small-Intestine Dysbiosis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/VJDZ-7B52. http://resolver.caltech.edu/CaltechTHESIS:10012019-095132591

Abstract

Our appreciation of the role of human-associated microbial communities in the context of human health and disease has grown dramatically in the past two decades, with modern research tools enabling deeper insights into the mechanisms of host-microbial interactions. The elusive notion of dysbiosis, a state of microbial imbalance related to a disease, has achieved widespread distribution across popular, scientific, and medical literature (on September 16, 2019 PubMed search yielded 6,064 records of scientific and medical publications containing this keyword). The conventional wisdom further narrows down the definition and understanding of dysbiosis towards a compositional "imbalance" of the microbiota (a community of all microorganisms inhabiting human body). There exists an additional and frequently overlooked aspect of microbial imbalance in the context of the human gastrointestinal system, something that we can define as a "spatial imbalance": a state of the microbial community in the host gastrointestinal system where even a "healthy" and "balanced" microbiota may be associated with or causative of a disease by being present in sections of the gastrointestinal tract where it is not "supposed" to be, with the most prominent example being small intestinal bacterial overgrowth (SIBO). This thesis describes the progress in the development of analytical tools (quantitative microbiome profiling described in Chapter I) and refinement of animal mouse models (non-coprophagic mouse model described in Chapter II) for exploring the normal function of small-intestine microbiota in health and for dissecting the mechanisms of emergence and the persistence of the small-intestine dysbiosis (SIBO) in the future.

Thesis Files