Abstract

Dietary Fiber, Bile Acids, and the Microbiome: A Multi-Omics Look at Fiber-Induced Cholesterol Mitigation
Michael Tang, Samuel Lancaster Ph.D., Brittany Lee Ph.D., Michael Snyder Ph.D.

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The Food and Drug Administration has affirmed the ability of fiber to decrease the risk of cardiovascular disease (CVD) and promote gastrointestinal homeostasis. To elucidate the role of soluble fibers in cholesterol mitigation, we used multi-omics data analysis to capture the biological signatures of participants when given fibers arabinoxylan (AX), long chain inulin (LCI), and a mixture of AX and LCI with beta-glucans, gluco-mannans, and resistant starch (Mix), in turn, over the course of a longitudinal study. Lipid panel results affirmed that AX and Mix can consistently reduce low-density lipoprotein and total cholesterol, solidifying the inverse relationship between soluble fibers and cardiovascular disease risk. In contrast, LCI supplementation lead to no significant change. We found significant upregulation in several primary and secondary bile acids and gut microbiome genera associated with cholesterol reduction or antioxidative effects, potentially counteracting the reactive oxygen species produced by increased secondary bile acid metabolism. We mapped inter-omic correlation networks and found gut bacteria of interest correlating against cholesterol but with several bile acids, supporting this indirect fiber-cholesterol link through the metabolome. The discovery of these novel associations between bile acids, gut microbiota, and lipids allowed us to model a potential underlying mechanism of cholesterol mitigation via phenol-bound fiber sequestration and microbiome-induced bile acid excretion. This opens up a promising area for further investigation to optimize fiber supplementation and offer alternatives to conventional treatments of CVD, and demonstrates the unprecedented capacity of multi-omics datasets to capture complete biological signatures and metabolic interactions.