Abstract 609: Plasma Carnitine is Associated with Gut Microbiome Composition, Diet, and Markers of Cardiometabolic Health

Cardiometabolic health is influenced by both diet and gut microbiome composition, however mechanisms remain unclear. The dietary-derived metabolite carnitine has been of particular interest for its potential gut microbial-mediated relationship to atherosclerosis. Using plasma carnitine as an intermediate probe, we examined the relationship between diet, gut microbiome composition, circulating metabolite levels, and measurements of cardiometabolic health. Samples (blood, stool) and data (diet, anthropometrics) were collected from 136 healthy subjects. Purified stool 16S V4 DNA was sequenced (Illumina MiSeq, 300bp paired-end reads, ~150,000 reads/sample). Plasma carnitine was analyzed by mass spectrometry. There were several dietary components significantly associated with plasma carnitine, with an overall pattern of a diet rich in animal products and refined carbohydrates (dairy, processed meats, non-whole grains and starchy vegetables) associated with higher carnitine, while monounsaturated fat intake was associated with lower carnitine. Plasma carnitine was significantly negatively correlated with several bacterial genera including Blautia (r=-0.3 p=0.001), Parabacteroides (r=-0.2, p=0.03), and Coprococcus (r=-0.389, p<0.001). Carnitine levels above the median were associated with increases in cardiometabolic risk factors including higher systolic blood pressure (SBP, 118 vs 111 mmHg, p=0.014), BMI (27 vs. 24 kg/m 2 , p=0.002), waist-hip ratio (WHR, 0.85 vs 0.8, p=0.001) as well as higher levels of blood components associated with cardiovascular risk, including circulating monocytes (p=0.007) and hemoglobin (p=0.006). Both diet and microbiome composition also associated with several risk markers (WHR, SBP, hemoglobin), albeit to a lesser extent than plasma carnitine. In conclusion, we provide evidence for inter-related relationships between diet, microbiome composition, circulating metabolites, and markers of cardiometabolic health.

Riboflavin Supplementation Improves Energy Metabolism in Mice Exposed to Acute Hypoxia

This study investigated the effects of riboflavin on energy metabolism in hypoxic mice. Kunming mice were fed diets containing riboflavin at doses of 6, 12, 24 and 48 mg/kg, respectively for 2 weeks before exposure to a simulated altitude of 6000 m for 8 h. Changes of riboflavin status and energy metabolism were assessed biochemically. Simultaneously, a 1H nuclear magnetic resonance (NMR) based metabolomic technique was used to track the changes of plasma metabolic profiling. It was found that the content of hepatic riboflavin was decreased and erythrocyte glutathione activation coefficient was elevated significantly under hypoxic condition. Meanwhile, increased plasma pyruvate, lactate, β-hydroxybutyrate and urea, as well as decreased plasma carnitine were observed. Riboflavin supplementation improved riboflavin status remarkably in hypoxic mice and decreased plasma levels of pyruvate, free fatty acids and β-hydroxybutyrate significantly. Plasma carnitine was increased in response to riboflavin supplementation. Results obtained from 1H NMR analysis were basically in line with the data from biochemical assays and remarkable changes in plasma taurine, choline and some other metabolites were also indicated. It was concluded that riboflavin requirement was increased under acute hypoxic condition and riboflavin supplementation was effective in improving energy metabolism in hypoxic mice.