UNCOVERING NOVEL ROLES FOR THE GUT MICROBIOTA IN MODULATING DIET-DERIVED FAT
Access to this document is restricted. Some items have been embargoed at the request of the author, but will be made publicly available after the "No Access Until" date.
During the embargo period, you may request access to the item by clicking the link to the restricted file(s) and completing the request form. If we have contact information for a Cornell author, we will contact the author and request permission to provide access. If we do not have contact information for a Cornell author, or the author denies or does not respond to our inquiry, we will not be able to provide access. For more information, review our policies for restricted content.
Gut microbes take up and metabolize nutrients consumed in human diets, thereby modulating the effects of diet on host physiology. Past studies reveal roles for gut bacteria in processing dietary fats, but knowledge of how commensal bacteria influence the processing of dietary long-chain polyunsaturated fatty acids (LCPUFAs) and dietary choline is still limited. Omega-3 LCPUFA consumption reduces inflammation, and LCPUFA consumption in infancy is important for cognitive development. Although eicosapentaenoic acid (EPA) is a prominent anti-inflammatory omega-3 LCPUFA in infant and adult diets, the role of EPA consumption in infant health requires further investigation, and little is known about the ability of gut bacteria to take up and metabolize EPA. Understanding how gut bacteria influence dietary EPA processing would clarify whether microbiome composition should be taken into account when predicting health outcomes and maximizing health benefits associated with EPA consumption. Similarly, information on how gut bacteria modulate dietary choline processing is limited, with many studies focusing on bacterial production of trimethylamine from choline. Elucidating how gut microbes influence the production of other dietary choline-derived metabolites would indicate whether the microbiota contributes to physiological effects of choline consumption. This dissertation provides new information on how gut bacteria interact with LCPUFAs and choline. This information was uncovered using an experimental workflow titled Bioorthogonal Labeling-Sort-Sequence-Spectrometry, which utilizes bioorthogonal labeling to identify bacterial species capable of taking up specific nutrients and metabolites bacteria produce from those nutrients. Investigations into microbe-LCPUFA interactions reveal the identity of gut bacteria that take up EPA and reveal novel metabolites produced by gut bacteria from EPA. Bacterial EPA metabolites, along with a previously characterized bacterial LA metabolite, were detected in stool from human infants, indicating gut bacterial LCPUFA metabolism is relevant to infants. Investigations into microbe-choline interactions reveal gut bacterium Limosilactobacillus reuteri modulates phosphatidylcholine metabolites derived from dietary choline in mice. Novel metabolites produced by L. reuteri from choline are also reported. In addition to expanding knowledge of gut microbe interactions with LCPUFAs and choline, this research shares experimental and analytical approaches that can be repurposed to investigate other microbe-nutrient interactions.