Characterize novel interactions between dietary lipid and the gut microbiome
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Dietary lipids are major sources of energy and bioactive signals throughout life, yet we still lack the mechanistic information to precisely personalize recommendations of these dietary macronutrients to support human health and ameliorate disease. Recent advances in chemical biology and lipidomics have improved our ability to examine how specific dietary lipids influence human biology. Emerging evidence suggests that one important but underexplored way that lipids affect host health is through the gut microbiome metabolism, which can transform dietary lipids into metabolites that affect host physiology. For example, certain commensal bacteria convert dietary cholesterol into coprostanol, a metabolite that is less absorbable than cholesterol and may offer therapeutic potential for cardiovascular disease. Despite these advances, direct interactions between dietary lipids and gut microbes remain poorly understood, and most diet-dependent microbial lipid metabolites have not been identified or functionally characterized.This dissertation investigates how common dietary lipids interact with the gut microbiome, from bacterial metabolism to host physiological responses. In Chapter 2, I applied a bioorthogonal labeling workflow developed in our lab to identify direct interactions between dietary saturated fatty acids and gut microbes, revealing novel microbiome-derived metabolites. Chapter 3 identified new gut microbial metabolites derived from polyunsaturated fatty acids (PUFA) and examines how PUFA supplementation shapes the gut microbiome and metabolome in the context of infant nutrition. Chapter 4 explored how lipid-producing commensal bacteria influence skin physiology and barrier function. Chapter 5 described a new global quantification method for alkyne-containing metabolites to support future studies of microbial metabolite transfer from the gut to host tissues. Together, this work expands our understanding of how dietary lipids are transformed by gut microbes into biologically active molecules that influence host physiology. It also lays new conceptual and methodological foundations for studying lipid-microbiome-host interactions in the context of precision nutrition.