Location: Obesity and Metabolism Research
Project Number: 2032-10700-003-034-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Apr 1, 2026
End Date: Mar 31, 2028
Objective:
Determine if a Mediterranean-style Dietary Guidelines diet improves liver fat and reduces plasma TMAO and risk for metabolic disease, and examine diet-microbiome-cardiometabolic health relationships.
Approach:
To establish causality between diet-induced microbiome changes and metabolic outcomes, we perform fecal microbiome adoptive transfers into germ-free or antibiotic-treated mice. Fecal samples collected pre- and post-Mediterranean diet intervention are transferred via oral gavage, isolating microbiome effects from direct dietary impacts.
Recipient mice are assessed for hepatic steatosis (histology, triglyceride quantification), plasma and cecal TMAO concentrations (LC-MS), and microbial community composition (16S rRNA sequencing). Functional analyses include microbial TMA production genes (cutC/D) via qPCR/metagenomics and hepatic inflammation markers (TNF-a, IL-6, macrophages).
This approach directly tests whether Mediterranean diet-induced microbiome changes causally mediate improvements in liver fat and TMAO metabolism. Results identify targetable microbiome features for precision nutrition interventions addressing metabolic syndrome and cardiovascular disease risk, bridging human dietary data with mechanistic understanding of gut-liver-cardiovascular interactions.