Characterizing the Mouse Gut Microbiome and Improving Mouse Gut-Derived Microbial Communities for Mouse Model Studies

Abstract

Reproducibility of mouse model studies remains a problem amongst researchers. Consequently, characterizing the mouse gut microbiota has become a necessary task. At present, the mouse gut microbiota is largely uncharacterized, both taxonomically and functionally. As such, shaping forces which may influence the gut microbial composition, such as environmental factors, like chow and housing, are not completely understood. In addition, existing mouse models do not completely capture the known complexity and diversity of the mouse gut microbiota. As such, this thesis sought to investigate the hypothesis that there are shared microorganisms within the gut microbiomes of SPF mice despite environmental factors and inclusion of these shared core microorganisms can improve current defined communities used in mouse model studies. To address this, three main objectives were outlined for mouse gut-derived microbial communities from various mouse samples, as well as for evaluating the inclusion of novel isolates within the commonly used defined mouse-derived microbial ecosystem Oligo-Mouse-Microbiota-12 (Oligo-MM12). A suitable model system, including the coupling of an in vitro bioreactor modeling the mouse colonic environment and microbial communities derived from mouse pellet samples enabled dissection of the microbial communities present within mice and determined which microorganisms are native to the mouse gut and their corresponding functionalities. Though a core microbiome was not uncovered in this study, additional species which were not previously characterized within the mouse gut were discovered. Additionally, in vitro investigation of the mouse gut metabolome presented findings highlighting differences in metabolite concentrations between genetic lines while uncovering lactate as a prevalent fermentative product. Finally, the addition of six novel Muribaculaceae isolates to Oligo-MM12 resulted in an altered metabolic signature that carried an increased number of anti-inflammatory metabolites compared to Oligo-MM12 alone. Overall, the studies in this thesis have considerably expanded our knowledge of the taxonomic and metabolic profiles of the mouse gut microbiota, and provides groundwork that potentiates improvement of mouse gut-derived microbial communities to be used in mouse model studies.