Choline is an essential nutrient crucial in synthesizing neurotransmitters, lipid transport, regulation of osmolyte levels, and one-carbon metabolism. The deficiency of choline can lead to several health issues, such as liver disease, muscle atrophy, and neurodegenerative diseases. The recommended daily choline intake may vary depending on age and genetics. Recently, it has been appreciated that the body’s physiological response to choline is dependent on the metabolic capacity of the gut microbiome. Gut microbes with the ability to transform choline to trimethylamine (TMA) via the CutC gene cluster are important modifiers of dietary choline intake. Despite the role of choline metabolizing microbes in contributing to processes ranging from cardiovascular function to body odor, dietary choline recommendations do not actively consider the significant and quantifiable role of gut microbes in interacting with diet-derived choline. Moreover, despite a well-defined role for gut microbes in modifying dietary choline through the production of TMA, choline is a versatile metabolite that has the potential to interact with the microbiome in a CutC-independent fashion to produce bioactive microbiome-derived metabolites other than TMA. The discovery of other choline-dependent microbiome-derived metabolites will help in our understanding of how choline consumption can have varied effects on host health that are highly specific to the personalized metabolic potential of one’s microbiome.

The following chapters explore the interactions between dietary choline and the gut microbiome. In Chapter 1, we employed a biorthogonal click chemistry-based workflow to identify novel gut microbes that utilize dietary choline. This approach led to discovering previously uncharacterized choline-utilizing gut microbes, including Limosilactobacillus reuteri (L. reuteri). In Chapter 2, we expanded upon this methodology to confirm the utilization of dietary choline by L. reuteri, both in vitro and in vivo. In addition, we used choline-sufficient and deficient rodent diets to characterize the effects of dietary choline-L. reuteri interaction on host physiology. This work identified novel gut microbes that utilize dietary choline and examined the effects of the choline-utilizing microbe L. reuteri on host physiology. The findings presented in this dissertation lay the groundwork for understanding how these newly identified choline-utilizing microbes influence dietary choline metabolism in the host and, in turn, how this affects their health.